2024-03-28T18:09:16Zhttp://oai.recercat.cat/request
oai:recercat.cat:2072/2216032014-09-10T22:35:58Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/221603Fmoc-2-Mercaptobenzothiazole (MBT), for the Introduction of the Fmoc Moiety Free of Side-ReactionsIsidro Llobet, AlbertJust Baringo, XavierEwenson, ArielÁlvarez Domingo, MercedesAlbericio Palomera, FernandoReaccions químiquesSíntesi de pèptidsChemical reactionsPeptide synthesisA double side-reaction, consisting in the formation of Fmoc--Ala-OH and Fmoc--Ala-AA-OH, during the preparation of Fmoc protected amino acids (Fmoc-AA-OH) with Fmoc-OSu is discussed. Furthermore, the new Fmoc-2-MBT reagent is proposed for avoiding these side-reactions as well as the formation of the Fmoc-dipeptides (Fmoc-AA-AA-OH) and even tripeptides, which is another important side-reaction when chloroformates such as Fmoc-Cl is used for the protection of the -amino function of the amino acids.WileyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionhttp://hdl.handle.net/2445/48634eng(c) Wiley, 2007info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2006882014-09-16T22:33:36Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/200688Estudio quimiotaxonomico del Thymus piperella L.Adzet Porredón, TomásPasset, J. (Jean)Taxonomia botànicaQuimiotaxonomiaPenínsula IbèricaBotanical taxonomyChemotaxonomyIberian PeninsulaRecientes investigaciones han puesto de relieve la existencia de 'razas químicas' en varias especies del género Thymus ( 1 ) (2) (3). El polimorfismo químico ha quedado bien demostrado en las labiadas. Los aceites esenciales, sustancias 'secundarias' de las plantas, son principios cuyos procesos biológicos de formación, es decir, la aptitud de cada individuo para que, en función de su patrimonio genético, sintetice unos determinados compuestos, tienen una señalada significación taxonómica.Consejo Superior de Investigaciones Científicas (CSIC)Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/30142engcc-by-nc (c) Consejo Superior de Investigaciones Científicas (CSIC), 1976info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc/3.0/es">http://creativecommons.org/licenses/by-nc/3.0/es</a>
oai:recercat.cat:2072/2216052014-11-01T23:11:21Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/221605p-Nitrobenzyloxycarbonyl (pNZ) as Temporary Na-Protecting Group for Mild Solid-Phase Peptide Synthesis. Avoiding Diketopiperazine and Aspartimide FormationIsidro Llobet, AlbertGuasch Camell, JuditÁlvarez Domingo, MercedesAlbericio Palomera, FernandoQuímica combinatòriaCombinatorial chemistryp-Nitrobenzyloxycarbonyl was used as temporary protecting group for the -amino function in solid-phase peptide synthesis. The corresponding derivatives are solids, easy to be synthesized, and perform well in the solid-phase mode. pNZ is removed in practical neutral conditions in the presence of catalytic amounts of acid. They are orthogonal with the most common protecting groups used in peptide chemistry. They are specially useful in combination with Fmoc chemistry to overcome those side reactions associated with the used of the piperidine such DKP and aspartiimide formation. The flexibility of pNZ can be very useful for the preparation of libraries of small organic molecules.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionhttp://hdl.handle.net/2445/48647eng(c) Wiley-VCH Verlag GmbH & Co. KGaA, 2005info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2216042015-01-23T23:27:57Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/221604Convergent Approaches for the Synthesis of the Anti-tumoral Peptide, Kahalalide F. Study of Orthogonal Protecting GroupsGracia, CarolinaIsidro Llobet, AlbertCruz, Luis J.Acosta, Gerardo A.Álvarez Domingo, MercedesCuevas, CarmenGiralt Lledó, ErnestAlbericio Palomera, FernandoPèptidsMedicaments antineoplàsticsProductes marins naturalsPeptidesAntineoplastic agentsMarine natural productsKahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show anti-tumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported. Here we describe several new improved synthetic routes based on convergent approaches with distinct orthogonal protection schemes for the preparation of Kahaladide analogues. These strategies allow a better control and characterization of the intermediates because more reactions are performed in solution. Five derivatives of Kahalalide F were synthesized using several convergent approaches.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/48635eng(c) American Chemical Society , 2006info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2454192015-03-18T23:31:08Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/245419Total synthesis of lamellarin D and analogs libraryÁlvarez Domingo, MercedesPla Queral, DanielOlsen, Christian A.Marchal, AntonioFrancesch, AndrésCuevas, CarmenAlbericio Palomera, FernandoCompostos heterocíclicsProductes naturals marinsAlcaloidesMedicaments antineoplàsticsHeterocyclic compoundsMarine natural productsAlkaloidsAntineoplastic agentsLarnellarins are a group of marine natural products isolated from the prosobranch mollusc Lamellaria sp., the ascidian Didemnum sp., and the sponge Dendrilla Cactos. Several of them exhibit interesting biological activities. Natural as well as synthetic lamellarins should be excellent candidates for the development of new drugs due to their unique skeletal structure and their important biological activities especially as antitumor agents. Lamelarin O has been recently characterized as a topoisomerase 1-targeted anti tumor agent. A variety of synthetic approaches have been developed for this family of alkaloids. Herein we describe a new route to the synthesis of Lamellarin D, from a methyl 2-pyrrolecarboxylate. Transformation of the starting material into the scaffold, a substituted 5,6-dihydropyrrolo (2,l a)isoquinoline (5,6-DHPl), was afforded by N-alkylation followed by intramolecular Heck cyclization. From this scaffold the synthetic strategy is based on two sequential regioselective bromination!Suzuki cross-coupling reactions which permitted the introduction of differently substituted aryl groups on positions 1 and 2 followed by oxidation, deprotection, and lactonization.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/61727eng(c) Álvarez Domingo et al., 2006info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2461532015-03-18T23:31:11Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/246153The synthesis of 1,2,3,6,6a,7-hexahydro-7-methyl-5-imino-1H-pyrrolo[1,2-c]imidazolo[5,4-b]indolePla Queral, DanielMills, KeithJoule, John A.Albericio Palomera, FernandoÁlvarez Domingo, MercedesSíntesi orgànicaMedicaments antineoplàsticsCompostos de nitrogenAziridinesÀcids nucleicsOrganic synthesisAntineoplastic agentsNitrogen compoundsAziridinesNucleic acidsN-3-(1-Methylindol-3-yl)propan-N-(2,2,2-trichloroethoxysulfonyl)guanidine was synthesized from 3-formyl-1-methylindole in six steps and subjected to conditions intended to convert the side-chain into a 2-iminotetrahydropyrimidine- containing product, of relevance to a possible synthesis of the aplicyanins. An alternative reaction course was observed, resulting in the formation of a new tetracyclic system.Michigan PublishingUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/62365engcc-by-nc (c) Pla Queral, Daniel et al., 2009info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc/3.0/es">http://creativecommons.org/licenses/by-nc/3.0/es</a>
oai:recercat.cat:2072/2496342015-05-04T22:18:58Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/249634Inserció laboral i qualitat de la ocupació en els ensenayments de pregrau de la Facultat de FarmàciaPallàs i Llibería, Mercè, 1964-Escolano Mirón, CarmenMéndez, JordiFerrer i Cervero, Virginia, 1962-Transició a la vida activaEstudiantsFarmàciaSchool-to-work transitionStudentsPharmacyUniversitat de BarcelonaL’Agència per a la Qualitat del Sistema Universitari (AQU) i les universitats catalanes, per tal de copsar el grau d’inserció laboral dels titulats, realitzen una enquesta amb una periodicitat triennal. L’enquesta permet conèixer no només la inserció sinó qüestions més especifiques com la temporalitat, la satisfacció respecte de la formació rebuda i el lloc de treball i el nivell de retribució, entre d’altres. L’anàlisi de les dades de les titulacions de la Facultat de Farmàcia, és d’interès per al disseny d’estratègies i d’activitats de orientació professional al centre.Universitat de Barcelonainfo:eu-repo/semantics/conferenceObjecthttp://hdl.handle.net/2445/65312catcc by (c) Pallàs i Llibería et al., 2015info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc-nd/3.0/es/">http://creativecommons.org/licenses/by-nc-nd/3.0/es/</a>
oai:recercat.cat:2072/2384662015-06-04T22:12:51Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238466Dual inhibitors of beta-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidatesViayna, ElisabetSabaté Lagunas, RaimonMuñoz-Torrero López-Ibarra, DiegoAgregació (Química)Malaltia d'AlzheimerAmiloïdosiAggregation (Chemistry)Alzheimer's diseaseAmyloidosisNotwithstanding the functional role that the aggregates of some amyloidogenic proteins can play in different organisms, protein aggregation plays a pivotal role in the pathogenesis of a large number of human diseases. One of such diseases is Alzheimer"s disease (AD), where the overproduction and aggregation of the β-amyloid peptide (Aβ) are regarded as early critical factors. Another protein that seems to occupy a prominent position within the complex pathological network of AD is the enzyme acetylcholinesterase (AChE), with classical and non-classical activities involved at the late (cholinergic deficit) and early (Aβ aggregation) phases of the disease. Dual inhibitors of Aβ aggregation and AChE are thus emerging as promising multi-target agents with potential to efficiently modify the natural course of AD. In the initial phases of the drug discovery process of such compounds, in vitro evaluation of the inhibition of Aβ aggregation is rather troublesome, as it is very sensitive to experimental assay conditions, and requires expensive synthetic Aβ peptides, which makes cost-prohibitive the screening of large compound libraries. Herein, we review recently developed multi-target anti-Alzheimer compounds that exhibit both Aβ aggregation and AChE inhibitory activities, and, in some cases also additional valuable activities such as BACE-1 inhibition or antioxidant properties. We also discuss the development of simplified in vivo methods for the rapid, simple, reliable, unexpensive, and high-throughput amenable screening of Aβ aggregation inhibitors that rely on the overexpression of Aβ42 alone or fused with reporter proteins in Escherichia coli.Bentham Science PublishersUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/50684eng(c) Bentham Science Publishers, 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2513582015-06-25T22:15:09Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/251358Farmacología y toxicología en I+D+i: adquisición de competencias a través de un ejemplo de desarrollo de un fármacoAlegret i Jordà, MartaEscubedo Rafa, ElenaJaner, G.Llobet Mallafré, Joan M. (Joan Maria)Merlos Roca, ManuelPallàs i Llibería, Mercè, 1964-Competències transversalsEducació superiorEnsenyamentFarmacologiaToxicologiaCiències de la salutGeneric competencesHigher educationTeachingPharmacologyToxicologyMedical sciencesThe implementation of the subject Pharmacology and Toxicology in R+D+i in the Pharmacy Degree, has led to the launch of a new methodological approach and teaching performance with the aim of developing the generic skills of the University of Barcelona (e.g., self-learning, team-working). An additional objective was students' integration of knowledge from different subjects in the degree which form the basis of the preclinical and clinical development of a drug. For this purpose, the teaching strategy used in the development of the subject was based on: 1) re-developing the content that students had been taught previously or were being taught in the same semester as a part of other subjects, and framing them in the environment of the pharmaceutical industry, 2) introducing new and previously unseen contents to do with drug development and toxicology, 3) developing a battery of activities to be undertaken by teams of students relating to the R+D+i of a particular drug. During the development of these activities, students have to acquire generic skills in addition to the subject-specific skills. The results obtained from the student survey give us grounds for satisfaction and allow us to consider that we have reached the goal of improving students' learning in Pharmacology and Toxicology applied to drug development in the pharmaceutical world today.Universitat de BarcelonaUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/66049spacc-by-nc-nd (c) Universitat de Barcelona, 2013info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc-nd/3.0/es">http://creativecommons.org/licenses/by-nc-nd/3.0/es</a>
oai:recercat.cat:2072/2249112016-01-12T23:13:48Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/224911Fructose induces synthesis and reduces oxidation of liver fatty acids through ChREBP activationRebollo de Grado, AlbaBaena Muñoz, MiguelRoglans i Ribas, NúriaAlegret i Jordà, MartaLaguna Egea, Juan CarlosFructosaMalalties del fetgeÀcids grassosFructoseLiver diseasesFatty acidsIntroduction and aims. During last few decades, the prevalence of obesity, metabolic syndrome and insulin resistance, among other metabolic disturbances, has raised considerably in many countries worldwide. Environmental factors (diet, physical activity), in tandem with predisposing genetic factors, may be responsible for this trend. Along with an increase in total energy consumption during recent decades, there has also been a shift in the type of nutrients, with an increased consumption of fructose, largely attributable to a greater intake of beverages containing high levels of fructose...Sociedad Española de FarmacologíaUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/51004eng(c) Fundación Teófilo Hernando / Sociedad Española de Farmacología, 2012info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2712552017-02-01T23:51:09Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/271255Determinació de la tolerància gastro-intestinal de medicaments mitjançant la quantificació radioactiva de les microhemorràgies digestivesRimbau i Barreras, VíctorLópez, R.Torralba Rodríguez, AntonioBiocompatibilitatEfectes secundaris dels medicamentsFarmacologiaGastroenterologiaIsòtops radioactiusRates (Animals de laboratori)Animals de laboratoriHemorràgia gastrointestinalAgents antiinflamatorisBiocompatibilityDrug side effectsPharmacologyGastroenterologyRadioisotopesRats as laboratory animalsLaboratory animalsGastrointestinal hemorrhageAntiinflammatory agentsLes lesions gastro-intestinals (GI) són, probablement, un deis principals efectes secundaris de l'ús dels antiinflamatoris i de molts altres agents terapèutics. Malgrat que els mecanismes productors de les lesions no són plenament coneguts, el fet és que les intoleràncies existeixen i que cal valorar-les per a poder preparar productes més innocus i formes farmacèutiques més ben tolerades. Els mètodes més usats en l'estudi de les toleràncies digestives es fonamenten en la valoració «de visu» de les lesions produïdes en els estómacs deis animals tractats. Evidentment, aquests mètodes només poden donar informació dels danys gàstrics, quedant doncs completament desconeguts els efectes sobre la resta del tub digestiu. ...Acadèmia de Ciències Mèdiques i de la Salut de Catalunya i de BalearsUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/106275cat(c) Rimbau i Barreras, Víctor et al., 1982info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2074982017-05-23T04:54:46Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/207498Moths behaving like butterflies. Evolutionary loss of long range attractant pheromones in Castniid Moths: A Paysandisia archon modelSarto, VíctorAcín Viu, PatriciaRosell Pellisé, GlòriaQuero López, CarmenJiménez, Miquel A.Guerrero Pérez, ÁngelLepidòptersEvolució molecularConducta sexual dels animalsFilogèniaFisiologia animalLepidopteraMolecular evolutionSexual behavior in animalsPhylogenyAnimal physiologyBackground: In the course of evolution butterflies and moths developed two different reproductive behaviors. Whereas butterflies rely on visual stimuli for mate location, moths use the"female calling plus male seduction" system, in which females release long-range sex pheromones to attract conspecific males. There are few exceptions from this pattern but in all cases known female moths possess sex pheromone glands which apparently have been lost in female butterflies. In the day-flying moth family Castniidae ("butterfly-moths"), which includes some important crop pests, no pheromones have been found so far. Methodology/Principal Findings: Using a multidisciplinary approach we described the steps involved in the courtship of P. archon, showing that visual cues are the only ones used for mate location; showed that the morphology and fine structure of the antennae of this moth are strikingly similar to those of butterflies, with male sensilla apparently not suited to detect female-released long range pheromones; showed that its females lack pheromone-producing glands, and identified three compounds as putative male sex pheromone (MSP) components of P. archon, released from the proximal halves of male forewings and hindwings. Conclusions/Significance: This study provides evidence for the first time in Lepidoptera that females of a moth do not produce any pheromone to attract males, and that mate location is achieved only visually by patrolling males, which may release a pheromone at short distance, putatively a mixture of Z,E-farnesal, E,E-farnesal, and (E,Z)-2,13-octadecadienol. The outlined behavior, long thought to be unique to butterflies, is likely to be widespread in Castniidae implying a novel, unparalleled butterfly-like reproductive behavior in moths. This will also have practical implications in applied entomology since it signifies that the monitoring/control of castniid pests should not be based on the use of female-produced pheromones, as it is usually done in many moths.Public Library of Science (PLoS)Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/34014engcc-by (c) Sarto, Víctor et al., 2012info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2817992017-05-23T04:54:56Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/281799A General Synthetic Route to Enantiopure 5-Substituted cis-DecahydroquinolinesAmat Tusón, MercedesFabregat, RobertGriera Farres, RosaBosch Cartes, JoanQuinolonesSíntesi orgànicaLactamesReacció d'oxidació-reduccióQuinolone antibacterial agentsOrganic synthesisLactamsOxidation-reduction reactionA practical synthetic route to enantiopure 5-substituted cisdecahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of 2-substituted 6-oxocyclohexenepropionates 2 with (R)-phenylglycinol, the stereoselective hydrogenation of the resulting unsaturated tricyclic lactams, and the stereoselective reductive cleavage of the oxazolidine ring.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/108263eng(c) American Chemical Society , 2009info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2110412017-05-23T04:55:12Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/211041Neuronal nicotinic receptors as new targets foramphetamine-induced oxidative damage and neurotoxicityPubill Sánchez, DavidGarcia Ratés, SaraCamarasa García, JordiEscubedo Rafa, ElenaÈxtasi (Droga)Receptors nicotínicsAmfetaminesNeurotoxicologiaEcstasy (Drug)Nicotinic receptorsAmphetaminesNeurotoxicologyAmphetamine derivatives such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are drugs widely abused in a recreational context. This has led to concern because of the evidence that they are neurotoxic in animal models and cognitive impairments have been described in heavy abusers. The main targets of these drugs are plasmalemmal and vesicular monoamine transporters, leading to reverse transport and increased monoamine efflux to the synapse. As far as neurotoxicity is concerned, increased reactive oxygen species (ROS) production seems to be one of the main causes. Recent research has demonstrated that blockade of 7 nicotinic acetylcholine receptors (nAChR) inhibits METH- and MDMA-induced ROS production in striatal synaptosomes which is dependent on calcium and on NO-synthase activation. Moreover, 7 nAChR antagonists (methyllycaconitine and memantine) attenuated in vivo the neurotoxicity induced by METH and MDMA, and memantine prevented the cognitive impairment induced by these drugs. Radioligand binding experiments demonstrated that both drugs have affinity to 7 and heteromeric nAChR, with MDMA showing lower Ki values, while fluorescence calcium experiments indicated that MDMA behaves as a partial agonist on 7 and as an antagonist on heteromeric nAChR. Sustained Ca increase led to calpain and caspase-3 activation. In addition, modulatory effects of MDMA on 7 and heteromeric nAChR populations have been found.MDPI PublishingUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/43290engcc-by (c) Pubill Sánchez, David et al., 2011info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2111682017-05-23T04:55:14Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/2111683,4-Methylenedioxy-methamphetamine induces in vivo regional up-regulation of central nicotinic receptors in rats and potentiates the regulatory effects of nicotine on these receptorsPubill Sánchez, DavidGarcia Ratés, SaraCamarasa García, JordiEscubedo Rafa, ElenaÈxtasi (Droga)Receptors nicotínicsAmfetaminesNicotinaEcstasy (Drug)Nicotinic receptorsAmphetaminesNicotineNicotine (NIC), the main psychostimulant compound of smoked tobacco, exerts its effects through activation of central nicotinic acetylcholine receptors (nAChR), which become up-regulated after chronic administration. Recent work has demonstrated that the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) has affinity for nAChR and also induces up-regulation of nAChR in PC 12 cells. Tobacco and MDMA are often consumed together. In the present work we studied the in vivo effect of a classic chronic dosing schedule of MDMA in rats, alone or combined with a chronic schedule of NIC, on the density of nAChR and on serotonin reuptake transporters. MDMA induced significant decreases in [3H]paroxetine binding in the cortex and hippocampus measured 24 h after the last dose and these decreases were not modified by the association with NIC. In the prefrontal cortex, NIC and MDMA each induced significant increases in [3H]epibatidine binding (29.5 and 34.6%, respectively) with respect to saline-treated rats, and these increases were significantly potentiated (up to 72.1%) when the two drugs were associated. Also in this area, [3H]methyllycaconitine binding was increased a 42.1% with NIC + MDMA but not when they were given alone. In the hippocampus, MDMA potentiated the a7 regulatory effects of NIC (raising a 25.5% increase to 52.5%) but alone was devoid of effect. MDMA had no effect on heteromeric nAChR in striatum and a coronal section of the midbrain containing superior colliculi, geniculate nuclei, substantia nigra and ventral tegmental area. Specific immunoprecipitation of solubilised receptors suggests that the up-regulated heteromeric nAChRs contain a4 and b2 subunits. Western blots with specific a4 and a7 antibodies showed no significant differences between the groups, indicating that, as reported for nicotine, up-regulation caused by MDMA is due to post-translational events rather than increased receptor synthesis.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/43395eng(c) Elsevier B.V., 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2111692017-05-23T04:55:15Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/211169Operacions bàsiques al laboratori químic en xarxa. Una nova eina per a estudiants i professorsAngurell Purroy, InmaculadaCaubet Marín, AmparoSeco, Miquel (Seco García)Casamitjana i Badia, NúriaDinarès Milà, M. ImmaculadaLlor Brunés, NúriaMuñoz-Torrero López-Ibarra, DiegoPérez García, M. Lluïsa (Maria Lluïsa)Pujol Dilmé, M. DolorsRosell Pellisé, GlòriaNicolás Galindo, ErnestoVelasco Castrillo, DoloresManuals de laboratoriAutoaprenentatgeLaboratoris químicsLaboratory manualsSelf-cultureChemical laboratoriesUn conjunt de professors de les facultats de Química i Farmàcia de la Universitat de Barcelona hem elaborat un material docent en suport electrònic, d"accés lliure a la xarxa, que descriu el procediment pràctic de diverses operacions bàsiques de treball al laboratori químic. L"objectiu principal és crear un material docent que serveixi de suport a l"aprenentatge dels estudiants i a la tasca docent del professorat involucrat en l"ensenyament del treball pràctic en l"etapa d"inici dels estudis universitaris.Institut d'Estudis CatalansUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/43412catcc-by-nc-nd (c) Angurell Purroy, Inmaculada et al., 2010info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc-nd/3.0/es">http://creativecommons.org/licenses/by-nc-nd/3.0/es</a>
oai:recercat.cat:2072/2198692017-05-23T04:55:19Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/219869An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'López-Arnau, RaúlMartínez-Clemente, JoséCarbó Banús, Marcel·líPubill Sánchez, DavidEscubedo Rafa, ElenaCamarasa García, JordiAmfetaminesFarmacocinèticaRates (Animals de laboratori)Locomoció animalAmphetaminesPharmacokineticsRats as laboratory animalsAnimal locomotionMaterial and methods. Methylone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (15 and 30 mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results. Oral administration of methylone induced a dose-dependent increase in locomotor activity in rats. The plasma concentrations after i.v. administration were described by a two-compartment model with distribution and terminal elimination phases of α = 1.95 h− 1 and β = 0.72 h− 1. For oral administration, peak methylone concentrations were achieved between 0.5 and 1 h and fitted to a flip-flop model. Absolute bioavailability was about 80% and the percentage of methylone protein binding was of 30%. A relationship between methylone brain levels and free plasma concentration yielded a ratio of 1.42 ± 0.06, indicating access to the central nervous system. We have identified four Phase I metabolites after oral administration. The major metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a demethylenate intermediate. Discussion. Pharmacokinetic and pharmacodynamic analysis of methylone showed a correlation between plasma concentrations and enhancement of the locomotor activity. A contribution of metabolites in the activity of methylone after oral administration is suggested. Present results will be helpful to understand the time course of the effects of this drug of abuse in humans.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/47623eng(c) Elsevier B.V., 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2249092017-05-23T04:55:21Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/224909Depression-like behavior is dependent on age in male SAMP8 micePérez-Cáceres, D.Ciudad Roberts, AndrésRodrigo i Calduch, Ma. TeresaPubill Sánchez, DavidCamins Espuny, AntoniCamarasa García, JordiEscubedo Rafa, ElenaPallàs i Llibería, Mercè, 1964-EnvellimentDepressió psíquicaEtologiaRatolins (Animals de laboratori)AgingMental depressionAnimal behaviorMice (Laboratory animals)Aging is associated with an increased risk of depression in humans. To elucidate the underlying mechanisms of depression and its dependence on aging, here we study signs of depression in male SAMP8 mice. For this purpose, we used the forced swimming test (FST). The total floating time in the FST was greater in SAMP8 than in SAMR1 mice at 9 months of age; however, this difference was not observed in 12-month-old mice, when both strains are considered elderly. Of the two strains, only the SAMP8 animals responded to imipramine treatment. We also applied the dexamethasone suppression test (DST) and studied changes in the dopamine and serotonin (5-HT) uptake systems, the 5-HT2a/2c receptor density in the cortex, and levels of TPH2. The DST showed a significant difference between SAMR1 and SAMP8 mice at old age. SAMP8 exhibits an increase in 5-HT transporter density, with slight changes in 5-HT2a/2c receptor density. In conclusion, SAMP8 mice presented depression-like behavior that is dependent on senescence process, because it differs from SAMR1, senescence resistant strain.Springer Science + Business MediaUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/49903eng(c) Springer Science + Business Media, 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2386412017-05-23T04:55:28Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238641A simple halide-to-anion exchange method for heteroaromatic salts and ionic liquidsAlcalde Pais, Ma. Ermitas (María de las Ermitas)Dinarès Milà, M. ImmaculadaIbáñez Jiménez, AnnaMesquida Estévez, Ma. NeusSalsSolucions iòniquesCompostos heterocíclicsSaltsIonic solutionsHeterocyclic compoundsA broad and simple method permitted halide ions in quaternary heteroaromatic and ammonium salts to be exchanged for a variety of anions using an anion exchange resin (A− form) in non-aqueous media. The anion loading of the AER (OH− form) was examined using two different anion sources, acids or ammonium salts, and changing the polarity of the solvents. The AER (A− form) method in organic solvents was then applied to several quaternary heteroaromatic salts and ILs, and the anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities. Relying on the hydrophobicity of the targeted ion pair for the counteranion swap, organic solvents with variable polarity were used, such as CH3OH, CH3CN and the dipolar nonhydroxylic solvent mixture CH3CN:CH2Cl2 (3:7) and the anion exchange was equally successful with both lipophilic cations and anions.MDPI PublishingUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/50799engcc-by (c) Alcalde Pais, Ma. Ermitas (María de las Ermitas) et al., 2012info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2273572017-05-23T04:55:32Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/227357Metabolic alterations and increased liver mTOR expression precede the development of autoimmune disease in a murine model of lupus erythematosusVilà Prats, LaiaRoglans i Ribas, NúriaBaena Muñoz, MiguelBarroso Fernández, EmmaAlegret i Jordà, MartaMerlos Roca, ManuelLaguna Egea, Juan CarlosLupus eritematósMalalties autoimmunitàriesMalalties del fetgeSíndrome metabòlicaProteïnes quinasesCitoquinesRatolins (Animals de laboratori)Lupus erythematosusAutoimmune diseasesLiver diseasesMetabolic syndromeProtein kinasesCytokinesMice (Laboratory animals)Although metabolic syndrome (MS) and systemic lupus erythematosus (SLE) are often associated, a common link has not been identified. Using the BWF1 mouse, which develops MS and SLE, we sought a molecular connection to explain the prevalence of these two diseases in the same individuals. We determined SLE- markers (plasma anti-ds-DNA antibodies, splenic regulatory T cells (Tregs) and cytokines, proteinuria and renal histology) and MS-markers (plasma glucose, non-esterified fatty acids, triglycerides, insulin and leptin, liver triglycerides, visceral adipose tissue, liver and adipose tissue expression of 86 insulin signaling-related genes) in 8-, 16-, 24-, and 36-week old BWF1 and control New-Zealand-White female mice. Up to week 16, BWF1 mice showed MS-markers (hyperleptinemia, hyperinsulinemia, fatty liver and visceral adipose tissue) that disappeared at week 36, when plasma anti-dsDNA antibodies, lupus nephritis and a pro-autoimmune cytokine profile were detected. BWF1 mice had hyperleptinemia and high splenic Tregs till week 16, thereby pointing to leptin resistance, as confirmed by the lack of increased liver P-Tyr-STAT-3. Hyperinsulinemia was associated with a down-regulation of insulin related-genes only in adipose tissue, whereas expression of liver mammalian target of rapamicyn (mTOR) was increased. Although leptin resistance presented early in BWF1 mice can slow-down the progression of autoimmunity, our results suggest that sustained insulin stimulation of organs, such as liver and probably kidneys, facilitates the over-expression and activity of mTOR and the development of SLE.Public Library of Science (PLoS)Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/52919engcc-by (c) Vilà Prats, Laia et al., 2012info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2855492017-05-23T04:55:33Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/285549Protracted treatment with MDMA induces heteromeric nicotinic receptor up-regulation in rat brain: an autoradiography study.Ciudad Roberts, AndrésCamarasa García, JordiEscubedo Rafa, ElenaPubill Sánchez, DavidCompostos heterocíclicsÈxtasi (Droga)AmfetaminesReceptors nicotínicsRates (Animals de laboratori)Heterocyclic compoundsEcstasy (Drug)AmphetaminesNicotinic receptorsRats as laboratory animalsPrevious studies indicate that 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy) can induce heteromeric nicotinic acetylcholine receptor (nAChR, mainly of α4β2 subtype) up-regulation. In this study we treated Sprague-Dawley rats twice-daily for 10 days with either saline or MDMA (7 mg/kg) and killed them on day 11 to perform [125I]epibatidine binding autoradiograms on serial coronal slices. Results showed significant increases in nAChR density in the substantia nigra, ventral tegmental area, nucleus accumbens, olfactory tubercle, anterior caudate-putamen, somatosensory cortex, motor cortex, auditory cortex, retrosplenial cortex, laterodorsal thalamus nuclei, amygdala, postsubiculum and pontine nuclei. These increases ranged from 3% (retrosplenial cortex) to 30 and 33% (amygdala and substantia nigra). No increased α4 subunit immunoreactivity was found in up-regulated areas compared with saline-treated rats, suggesting a post-translational mechanism as occurs with nicotine. The percentage of up-regulation correlated positively with the density of serotonin transporters, according to the serotonergic profile of MDMA. The heteromeric nAChR increase in concrete areas could account, at least in part, for the reinforcing, sensitizing and psychiatric disorders observed after long-term treatment with MDMA.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/53223eng(c) Elsevier B.V., 2014info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2394422017-05-23T04:55:35Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/239442Oxidative stress in aging: advances in proteomic approachesOrtuño-Sahagún, DanielPallàs i Llibería, Mercè, 1964-Rojas-Mayorquín, Argelia E.EnvellimentProteòmicaEstrès oxidatiuAgingProteomicsOxidative stressAging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual"s Quality of Life (QOL). Although extensive research efforts in recent years have been made, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging process. Additionally, the relevance of the oxidative stress factors is discussed. Emphasis is placed on postmitotic tissues, such as neuronal, muscular, and red blood cells, which appear to be those most frequently studied with respect to aging. Additionally, models for the study of aging are discussed in a number of organisms, such as Caenorhabditis elegans, senescence-accelerated probe-8 mice (SAMP8), naked mole-rat (Heterocephalus glaber), and the beagle canine. Proteomic studies in specific tissues and organisms have revealed the extensive involvement of reactive oxygen species (ROS) and oxidative stress in aging.HindawiUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/53944engcc-by (c) Ortuño-Sahagún, Daniel et al., 2014info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2309392017-05-23T04:55:36Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/230939Liquid fructose down-regulates liver insulin receptor substrate 2 and gluconeogeneic enzymes by modifying nutrient sensing factors in ratsRebollo de Grado, AlbaRoglans i Ribas, NúriaBaena Muñoz, MiguelPadrosa, AnnaSánchez Peñarroya, Rosa M.Merlos Roca, ManuelAlegret i Jordà, MartaLaguna Egea, Juan CarlosResistència a la insulinaFetgeFructosaInsulin resistanceLiverFructoseHigh consumption of fructose-sweetened beverages has been linked to a high prevalence of chronic metabolic diseases. We have previously shown that a short course of fructose supplementation as a liquid solution induces glucose intolerance in female rats. In the present work, we characterized the fructose-driven changes in the liver and the molecular pathways involved. To this end, female rats were supplemented or not with liquid fructose (10%, w/v) for 7 or 14 days. Glucose and pyruvate tolerance tests were performed, and the expression of genes related to insulin signaling, gluconeogenesis and nutrient sensing pathways was evaluated. Fructose-supplemented rats showed increased plasma glucose excursions in glucose and pyruvate tolerance tests and reduced hepatic expression of several genes related to insulin signaling, including insulin receptor substrate 2 (IRS-2). However, the expression of key gluconeogenic enzymes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was reduced. These effects were caused by an inactivation of hepatic forkhead box O1 (FoxO1) due to an increase in its acetylation state driven by a reduced expression and activity of sirtuin 1 (SIRT1). Further contributing to FoxO1 inactivation, fructose consumption elevated liver expression of the spliced form of X-box-binding-protein-1 as a consequence of an increase in the activity of the mammalian target of rapamycin 1 and protein 38-mitogen activated protein kinase (p38-MAPK). Liquid fructose affects both insulin signaling (IRS-2 and FoxO1) and nutrient sensing pathways (p38-MAPK, mTOR and SIRT1), thus disrupting hepatic insulin signaling without increasing the expression of key gluconeogenic enzymes.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/53946eng(c) Elsevier B.V., 2014info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2289562017-05-23T04:55:37Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/228956Liquid fructose downregulates SIRT1 expression and activity and impairs the oxidation of fatty acids in rat and human liver cellsRebollo de Grado, AlbaRoglans i Ribas, NúriaBaena Muñoz, MiguelSánchez Peñarroya, Rosa M.Merlos Roca, ManuelAlegret i Jordà, MartaLaguna Egea, Juan CarlosFructosaÀcids grassosFetgeFructoseFatty acidsLiverFructose ingestion is associated with the production of hepatic steatosis and hypertriglyceridemia. For fructose to attain these effects in rats, simultaneous induction of fatty acid synthesis and inhibition of fatty acid oxidation is required. We aimed to determine the mechanism involved in the inhibition of fatty acid oxidation by fructose and whether this effect occurs also in human liver cells. Female rats were supplemented or not with liquid fructose (10% w/v) for 7 or 14 days; rat (FaO) and human (HepG2) hepatoma cells, and human hepatocytes were incubated with fructose 25 mM for 24 h. The expression and activity of the enzymes and transcription factors relating to fatty acid β-oxidation were evaluated. Fructose inhibited the activity of fatty acid β-oxidation only in livers of 14-day fructose-supplemented rats, as well as the expression and activity of peroxisome proliferator activated receptor α (PPARα). Similar results were observed in FaO and HepG2 cells and human hepatocytes. PPARα downregulation was not due to an osmotic effect or to an increase in protein-phosphatase 2A activity caused by fructose. Rather, it was related to increased content in liver of inactive and acetylated peroxisome proliferator activated receptor gamma coactivator 1α, due to a reduction in sirtuin 1 expression and activity. In conclusion, fructose inhibits liver fatty acid oxidation by reducing PPARα expression and activity, both in rat and human liver cells, by a mechanism involving sirtuin 1 down-regulation.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/53947eng(c) Elsevier B.V., 2014info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2298722017-05-23T04:55:38Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/229872Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamicsMartínez-Clemente, JoséLópez-Arnau, RaúlCarbó Banús, Marcel·líPubill Sánchez, DavidCamarasa García, JordiEscubedo Rafa, ElenaAmfetaminesSistema nerviós centralCervellFarmacocinèticaEfectes fisiològicsDrogues de dissenyAmphetaminesCentral nervous systemBrainPharmacokineticsPhysiological effectDesigner drugsFe d'errates disponible a: http://dx.doi.org/10.1007/s00213-013-3283-6Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.Springer VerlagUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/53992eng(c) Springer Verlag, 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2098062017-05-23T04:55:39Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/209806A carboxylesterase, Esterase-6, modulates sensory physiological and behavioural response dynamics to pheromone in DrosophilaChertemps, ThomasFrançois, AdrienDurand, NicolasRosell Pellisé, GlòriaDekker, TeunLucas, PhilippeMaïbèche-Coisne, MartineDrosòfilaEnzimsFeromonesEtologiaOlorsEsterasesDrosophilaEnzymesPheromonesAnimal behaviorOdorsEsterasesBackground: Insects respond to the spatial and temporal dynamics of a pheromone plume, which implies not only a strong response to"odor on", but also to"odor off". This requires mechanisms geared toward a fast signal termination. Several mechanisms may contribute to signal termination, among which odorant-degrading enzymes. These enzymes putatively play a role in signal dynamics by a rapid inactivation of odorants in the vicinity of the sensory receptors, although direct in vivo experimental evidences are lacking. Here we verified the role of an extracellular carboxylesterase, esterase-6 (Est-6), in the sensory physiological and behavioral dynamics of Drosophila melanogaster response to its pheromone, cis-vaccenyl acetate (cVA). Est-6 was previously linked to post-mating effects in the reproductive system of females. As Est-6 is also known to hydrolyze cVA in vitro and is expressed in the main olfactory organ, the antenna, we tested here its role in olfaction as a putative odorant-degrading enzyme. Results: We first confirm that Est-6 is highly expressed in olfactory sensilla, including cVA-sensitive sensilla, and we show that expression is likely associated with non-neuronal cells. Our electrophysiological approaches show that the dynamics of olfactory receptor neuron (ORN) responses is strongly influenced by Est-6, as in Est-6° null mutants (lacking the Est-6 gene) cVA-sensitive ORN showed increased firing rate and prolonged activity in response to cVA. Est-6° mutant males had a lower threshold of behavioral response to cVA, as revealed by the analysis of two cVAinduced behaviors. In particular, mutant males exhibited a strong decrease of male-male courtship, in association with a delay in courtship initiation. Conclusions: Our study presents evidence that Est-6 plays a role in the physiological and behavioral dynamics of sex pheromone response in Drosophila males and supports a role of Est-6 as an odorant-degrading enzyme (ODE) in male antennae. Our results also expand the role of Est-6 in Drosophila biology, from reproduction to olfaction, and highlight the role of ODEs in insect olfaction. Keywords: carboxylesterase, esterase 6, olfaction, pheromone, signal terminationBioMed CentralUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/34504engcc-by (c) Chertemps, Thomas et al., 2012info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2334192017-05-23T04:55:40Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/233419Orthogonal protecting groups in the synthesis of tryptophanyl-hexahydropyrroloindolesRuiz Sanchis, PauSavina, Svetlana A.Acosta, Gerardo A.Albericio Palomera, FernandoÁlvarez Domingo, MercedesProductes naturals marinsQuímica heterocíclicaAminoàcidsSíntesi de pèptidsMarine natural productsHeterocyclic chemistryAmino acidsPeptide synthesisThe synthesis of various polycyclic systems containing a C3a-Ni bond between a hexahydropyrrolo[2,3-b]indole and an indole tryptophan is described here. A series of experiments were performed to determine the best combination of five orthogonal protecting groups and the best reaction conditions for formation of said bond, which is a common feature among many recently discovered marine natural products.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionhttp://hdl.handle.net/2445/54707eng(c) Wiley-VCH Verlag GmbH & Co. KGaA, 2012info:eu-repo/semantics/embargoedAccess
oai:recercat.cat:2072/2395572017-05-23T04:55:41Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/239557Total synthesis of aeruginazole ABruno, PaoloPeña, StellaJust Baringo, XavierAlbericio Palomera, FernandoÁlvarez Domingo, MercedesSíntesi de pèptidsQuímica heterocíclicaPeptide synthesisHeterocyclic chemistryThe first total synthesis of Aeruginazole A, prepared via a convergent strategy that involved both solid-phase peptide synthesis and solution phase chemistry and that enabled conservation of the stereochemistry of the intermediates, is reported.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/54698eng(c) American Chemical Society , 2011info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2855502017-05-23T04:55:44Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/285550Progress on LamellarinsPla Queral, DanielAlbericio Palomera, FernandoÁlvarez Domingo, MercedesProductes naturals marinsMarine natural productsThis review covers recent literature on the lamellarins, a family of marine natural products, and related analogs, encompassing synthetic strategies for total synthesis, structure-activity relationships (SAR), and studies on mechanisms of biological action, namely in the context of antitumor activity. It reviews work published from January 2008 to December 2010.Royal Society of ChemistryUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/54977eng(c) Pla Queral, Daniel et al., 2011info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2330842017-05-23T04:55:45Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/233084First enantioselective synthesis of isagarin, a natural product isolated from Pentas longiflora Oliv.Jacobs, JanClaessens, SvenMol, Eva deEl Hady, SamirMinguillón Llombart, CristinaÁlvarez Domingo, MercedesKimpe, Norbert deSíntesi asimètricaProductes naturalsAsymmetric synthesisNatural productsFor the first time, an enantioselective synthesis of both 1R,4S-isagarin 1a and 1S,4R-isagarin 1b was achieved starting from 1,4-dimethoxy-2-vinylnaphtalene 2. The key steps involve a Sharpless asymmetric dihydroxylation and reaction with an acetonylating pyridinium ylid.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/54980eng(c) Elsevier B.V., 2010info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2330852017-05-23T04:55:46Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/233085Recent advances in lamellarin alkaloids: isolation, synthesis and activityPla Queral, DanielAlbericio Palomera, FernandoÁlvarez Domingo, MercedesAlcaloidesProductes naturals marinsCompostos heterocíclicsMedicaments antineoplàsticsAlkaloidsMarine natural productsHeterocyclic compoundsAntineoplastic agentsLamellarins are a large family of marine alkaloids with potential anticancer activity that have been isolated from diverse marine organisms, mainly ascidians and sponges. All lamellarins feature a 3,4-diarylpyrrole system. Pentacyclic lamellarins, whose polyheterocyclic system has a pyrrole core, are the most active compounds. Some of these alkaloids are potently cytotoxic to various tumor cell lines. To date, Lam-D and Lam-H have been identified as lead compounds for the inhibition of topoisomerase I and HIV-1 integrase, respectively nuclear enzymes which are over-expressed in deregulation disorders. Moreover,these compounds have been reported for their efficacy in treatment of multi-drug resistant (MDR) tumors cells without mediated drug efflux, as well as their immunomodulatory activity and selectivity towards melanoma cell lines. This article is an overview of recent literature on lamellarins, encompassing their isolation, recent synthetic strategies for their total synthesis, the preparation of their analogs, studies on their mechanisms of action, and their structure-activity relationships (SAR).Bentham Science PublishersUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/54981eng(c) Bentham Science Publishers, 2008info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2330862017-05-23T04:55:48Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/233086Highly efficient, multigram and enantiopure synthesis of (S)-2-(2,4′-bithiazol-2-yl)pyrrolidineJust Baringo, XavierBruno, PaoloAlbericio Palomera, FernandoÁlvarez Domingo, MercedesProductes naturalsAntibiòticsSíntesi de pèptidsCompostos heterocíclicsEnantiòmersNatural productsAntibioticsPeptide synthesisHeterocyclic compoundsEnantiomers(S)-2-(4-Bromo-2,4"-bithiazole)-1-(tert-butoxycarbonyl)pyrrolidine ((S)-1) was obtained as a single enantiomer and in high yield by means of a two-step modified Hantzsch thiazole synthesis reaction when bromoketone 3 and thioamide (S)-4 were used. Further conversion of (S)-1 into trimethyltin derivative (S)-2 broadens the scope for further cross-coupling reactions.Elsevier LtdUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/54982eng(c) Elsevier Ltd, 2011info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2388482017-05-23T04:55:49Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238848Structure, bioactivity and synthesis of natural products with hexahydropyrrolo[2,3-b]indoleRuiz Sanchis, PauSavina, Svetlana A.Albericio Palomera, FernandoÁlvarez Domingo, MercedesAlcaloidesQuímica heterocíclicaProductes naturalsPèptidsAlkaloidsHeterocyclic chemistryNatural productsPeptidesResearch on natural products containing hexahydropyrrolo[2,3-b]indole (HPI) has dramatically increased during the past few years. Newly discovered natural products with complex structures and important biological activities have recently been isolated and synthesized. This review summarizes the structures, biological activities, and synthetic routes for natural compounds containing HPI, emphasizing the different strategies for assembling this motif. It covers a broad gamut of molecules, from small alkaloids to complex peptides.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/submittedVersionhttp://hdl.handle.net/2445/55003eng(c) Wiley-VCH, 2011info:eu-repo/semantics/embargoedAccess
oai:recercat.cat:2072/2371952017-05-23T04:55:50Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/237195Isolation, structural assignment and total synthesis of BarmumycinLorente, AdrianaPla Queral, DanielCañedo, Librada M.Albericio Palomera, FernandoÁlvarez Domingo, MercedesMedicaments antineoplàsticsProductes naturals marinsLactonesImidazolesAntineoplastic agentsMarine natural productsLactonesImidazolesBarmumycin was isolated from an extract of the marine actinomycete Streptomyces sp. BOSC-022A and found to be cytotoxic against various human tumor cell lines. Based on preliminary one- and two-dimensional 1H- and 13C-NMR spectra, the natural compound was initially assigned the structure of macrolactone-type compound 1, which was later prepared by two different routes. However, major spectroscopic differences between isolated barmumycin and 1 led to revision of the proposed structure as E-16. Based on synthesis of this new compound, and subsequent spectroscopic comparison of it to an authentic sample of barmumycin, the structure of the natural compound was indeed confirmed as that of E-16.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/55263eng(c) American Chemical Society , 2010info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2342672017-05-23T04:55:51Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/2342671,2-Dimethylindole-3-sulfonyl (MIS) as protecting group for the side chain of arginineIsidro Llobet, AlbertLatassa, DanielGiraud, MatthieuÁlvarez Domingo, MercedesAlbericio Palomera, FernandoSíntesi de pèptidsRadicals lliures (Química)Síntesi en fase sólidaPeptide synthesisFree radicals (Chemistry)Solid-phase synthesisThe protection of arginine (Arg) side chains is a crucial issue in peptide chemistry because of the propensity of the basic guanidinium group to produce side reactions. Currently, sulfonyl-type protecting groups, such as 2,2,5,7,8-pentamethylchroman (Pmc) and 2,2,4,6,7-pentamethyldihydrobenzofurane (Pbf), are the most widely used for this purpose. Nevertheless, Arg side chain protection remains problematic as a result of the acid stability of these two compounds. This issue is even more relevant in Arg-rich sequences, acid-sensitive peptides and large-scale syntheses. The 1,2-dimethylindole-3-sulfonyl (MIS) group is more acid-labile than Pmc and Pbf and can therefore be a better option for Arg side chain protection. In addition, MIS is compatible with tryptophan-containing peptides.Royal Society of ChemistryUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/55265eng(c) Isidro Llobet, Albert et al., 2009info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2342682017-05-23T04:55:52Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/234268Preparation of penta-azole containing cyclopeptides: challenges in macrocyclizationHernández Romero, DeliaRiego, EstelaFrancesch, AndrésCuevas, CarmenAlbericio Palomera, FernandoÁlvarez Domingo, MercedesProductes naturalsPèptidsSíntesi orgànicaCompostos heterocíclicsNatural productsPeptidesOrganic synthesisHeterocyclic compoundsHerein is described the synthesis of several analogs of the natural product IB-01211 from concatenated azoles, via a biomimetic pathway based on cyclization-oxidation of serine containing peptides combined with the Hantzsch synthesis. The macrocyclization of rigid peptide compounds 1 and 2 to give IB-01211 and its epimer 12b was explored, and the results are compared here to those previously obtained for the macrocyclization of more flexible structures in the syntheses of YM-216391, telomestatin, and IB-01211. Lastly, the preliminary results of anti-tumor activity screening of the synthesized analogs are discussed.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/55267eng(c) Elsevier B.V., 2007info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2374652017-05-23T04:55:53Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/237465Novel synthesis of arylethynyl heterocylesSoley, RogerAlbericio Palomera, FernandoÁlvarez Domingo, MercedesSíntesi orgànicaCompostos heterocíclicsAcetilèOrganic synthesisHeterocyclic compoundsAcetyleneA new and easy synthesis of 2-arylethynyl-indole and 2-arylethynyl-pyrrole is described. N-deprotection and subsequent base-catalyzed elimination of N-tosylheteroaryl benzyl ketones are the key steps of the process.Georg Thieme VerlagUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/55503eng(c) Georg Thieme Verlag, 2007info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2379762017-05-23T04:55:54Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/237976Effects of a post-weaning cafeteria diet in young rats: metabolic syndrome, reduced activity and low anxiety-like behaviour.Lalanza, Jaume F.Caimari, AntoniBas, Josep Maria delTorregrosa, DanielCigarroa, IgorPallàs i Llibería, Mercè, 1964-Capdevila, LluísArola i Ferrer, LluísEscorihuela, Rosa M.AnsietatDietaObesitatPlasma sanguiniRates (Animals de laboratori)Síndrome metabòlicaAnxietyDietObesityBlood plasmaRats as laboratory animalsMetabolic syndromeAmong adolescents, overweight, obesity and metabolic syndrome are rapidly increasing in recent years as a consequence of unhealthy palatable diets. Animal models of diet-induced obesity have been developed, but little is known about the behavioural patterns produced by the consumption of such diets. The aim of the present study was to determine the behavioural and biochemical effects of a cafeteria diet fed to juvenile male and female rats, as well as to evaluate the possible recovery from these effects by administering standard feeding during the last week of the study. Two groups of male and female rats were fed with either a standard chow diet (ST) or a cafeteria (CAF) diet from weaning and for 8 weeks. A third group of males (CAF withdrawal) was fed with the CAF diet for 7 weeks and the ST in the 8th week. Both males and females developed metabolic syndrome as a consequence of the CAF feeding, showing overweight, higher adiposity and liver weight, increased plasma levels of glucose, insulin and triglycerides, as well as insulin resistance, in comparison with their respective controls. The CAF diet reduced motor activity in all behavioural tests, enhanced exploration, reduced anxiety-like behaviour and increased social interaction; this last effect was more pronounced in females than in males. When compared to animals only fed with a CAF diet, CAF withdrawal increased anxiety in the open field, slightly decreased body weight, and completely recovered the liver weight, insulin sensitivity and the standard levels of glucose, insulin and triglycerides in plasma. In conclusion, a CAF diet fed to young animals for 8 weeks induced obesity and metabolic syndrome, and produced robust behavioural changes in young adult rats, whereas CAF withdrawal in the last week modestly increased anxiety, reversed the metabolic alterations and partially reduced overweight.Public Library of Science (PLoS)Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/55848engcc-by (c) Lalanza, Jaume F. et al., 2014info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2380692017-05-23T04:55:55Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238069Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogsSísa, MiroslavPla Queral, DanielAltuna, MartaFrancesch, AndrésCuevas, CarmenAlbericio Palomera, FernandoÁlvarez Domingo, MercedesMedicaments antineoplàsticsSíntesi de fàrmacsAlcaloidesMetabòlits marinsAntineoplastic agentsDrug synthesisAlkaloidsMarine metabolitesThe first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and fourteen of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the acetyl group moiety on the imine nitrogen, and the bromine at position 5 of the indole, are both critical to activity.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/56023eng(c) American Chemical Society , 2009info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2380702017-05-23T04:55:56Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238070Lamellarin D bioconjugates II: synthesis and cellular internalization of dendrimer and nuclear location signal derivativesPla Queral, DanielMartí, M.Farrera Sinfreu, Josep MariaPulido, DanielFrancesch, AndrésCalvo, PilarCuevas, CarmenRoyo Expósito, MiriamAligué i Alemany, Rosa MariaAlbericio Palomera, FernandoÁlvarez Domingo, MercedesCompostos heterocíclicsMedicaments antineoplàsticsProductes naturals marinsTransport biològicIsoquinolinaHeterocyclic compoundsAntineoplastic agentsMarine natural productsBiological transportIsoquinolineThe design and synthesis of Lamellarin D conjugates with a nuclear localization signal peptide and a poly(ethylene glycol)-based dendrimer are described. Conjugates 1-4 were obtained in 8-84% overall yields from the corresponding protected Lamellarin D. Conjugates 1 and 4 are 1.4 to 3.3-fold more cytotoxic than the parent compound against three human tumor cell lines(MDA-MB-231 breast, A-549 lung, and HT-29 colon). Besides, conjugates 3, 4 showed a decrease in activity potency in BJ skin fibroblasts, a normal cell culture. Cellular internalization was analyzed and nuclear distribution pattern was observed for 4, which contains a nuclear localization signalling sequence.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/56025eng(c) American Chemical Society , 2009info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2380722017-05-23T04:55:58Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238072Synthesis and antitumor activity of mechercharmycin A analoguesHernández, DeliaAltuna, MartaCuevas, CarmenAligué i Alemany, Rosa MariaAlbericio Palomera, FernandoÁlvarez Domingo, MercedesCompostos heterocíclicsMedicaments antineoplàsticsSíntesi de pèptidsEspectroscòpia de ressonància magnètica nuclearHeterocyclic compoundsAntineoplastic agentsPeptide synthesisNuclear magnetic resonance spectroscopySeveral analogs of the cytotoxic thiopeptide IB-01211 or Mechercharmycin A (1) have been synthetized. The cytotoxicity of 1 and the synthetized analogs was evaluated against a panel of three human tumor cell lines. Thiopeptide 1 and the most active derivatives, 2 and 3c, were chosen for further studies like effects on cell cycle progression and induction of apoptosis. Interestingly, the inhibition of cell division and activation of a programmed cell death by apoptosis was detected.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/56045eng(c) American Chemical Society , 2008info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2381682017-05-23T04:55:59Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238168Dose and time-dependent selective neurotoxicity induced by mephedrone in mice.Martínez-Clemente, JoséLópez-Arnau, RaúlAbad, SoniaPubill Sánchez, DavidEscubedo Rafa, ElenaCamarasa García, JordiAmfetaminesLòbul frontalNeurotoxicologiaRatolins (Animals de laboratori)Sistema nerviós centralAmphetaminesFrontal lobeNeurotoxicologyMice (Laboratory animals)Central nervous systemMephedrone is a drug of abuse marketed as 'bath salts'. There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules. Schedule 1: four doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily doses of 25 mg/kg, for two consecutive days. All schedules induced, in some animals, an aggressive behavior and hyperthermia as well as a decrease in weight gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule 2) only a transient dopaminergic injury was found. In the weekend consumption pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss that was accompanied by a decrease in tyrosine hydroxylase and tryptophan hydroxylase 2 expression one week after exposition. Also, mephedrone induced a depressive-like behavior, as well as a reduction in striatal D2 density, suggesting higher susceptibility to addictive drugs. In cultured cortical neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using repeated doses for 2 days in an elevated ambient temperature we evidenced a loss of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers that suggest injuries at nerve endings.Public Library of Science (PLoS)Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/56203engcc-by (c) Martínez-Clemente, José et al., 2014info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2382312017-05-23T04:56:00Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238231Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin DPla Queral, DanielMarchal, AntonioOlsen, Christian A.Francesch, AndrésCuevas, CarmenAlbericio Palomera, FernandoÁlvarez Domingo, MercedesAlcaloidesProductes naturals marinsCompostos heterocíclicsMedicaments antineoplàsticsIsoquinolinaAlkaloidsMarine natural productsHeterocyclic compoundsAntineoplastic agentsIsoquinolineThe marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB- 231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data the SAR study concluded that more than 75% of the open-chain Lam-D analogs tested showed cytotoxicity in a low micromolar GI50 range.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/56314eng(c) American Chemical Society , 2006info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2098662017-05-23T04:56:01Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/209866The Interplay between NF-kappaB and E2F1 Coordinately Regulates Inflammation and Metabolism in Human Cardiac CellsPalomer Tarridas, Francesc XavierÁlvarez Guardia, DavidDavidson, Mercy M.Chan, Tung O.Feldman, Arthur M.Vázquez Carrera, ManuelCorMiocardiFisiologia cel·lularProteïnesTranscripció genèticaCèl·lules muscularsHeartMyocardiumCell physiologyProteinsGenetic transcriptionMuscle cellsPyruvate dehydrogenase kinase 4 (PDK4) inhibition by nuclear factor-κB (NF-κB) is related to a shift towards increased glycolysis during cardiac pathological processes such as cardiac hypertrophy and heart failure. The transcription factors estrogen-related receptor-α (ERRα) and peroxisome proliferator-activated receptor (PPAR) regulate PDK4 expression through the potent transcriptional coactivator PPARγ coactivator-1α (PGC-1α). NF-κB activation in AC16 cardiac cells inhibit ERRα and PPARβ/δ transcriptional activity, resulting in reduced PGC-1α and PDK4 expression, and an enhanced glucose oxidation rate. However, addition of the NF-κB inhibitor parthenolide to these cells prevents the downregulation of PDK4 expression but not ERRα and PPARβ/δ DNA binding activity, thus suggesting that additional transcription factors are regulating PDK4. Interestingly, a recent study has demonstrated that the transcription factor E2F1, which is crucial for cell cycle control, may regulate PDK4 expression. Given that NF-κB may antagonize the transcriptional activity of E2F1 in cardiac myocytes, we sought to study whether inflammatory processes driven by NF-κB can downregulate PDK4 expression in human cardiac AC16 cells through E2F1 inhibition. Protein coimmunoprecipitation indicated that PDK4 downregulation entailed enhanced physical interaction between the p65 subunit of NF-κB and E2F1. Chromatin immunoprecipitation analyses demonstrated that p65 translocation into the nucleus prevented the recruitment of E2F1 to the PDK4 promoter and its subsequent E2F1-dependent gene transcription. Interestingly, the NF-κB inhibitor parthenolide prevented the inhibition of E2F1, while E2F1 overexpression reduced interleukin expression in stimulated cardiac cells. Based on these findings, we propose that NF-κB acts as a molecular switch that regulates E2F1-dependent PDK4 gene transcription.Public Library of Science (PLoS)Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/34533engcc-by (c) Palomer Tarridas, Francesc Xavier et al., 2011info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2388492017-05-23T04:56:02Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/238849Thiopeptide antibiotics: retrospective and recent advancesJust Baringo, XavierAlbericio Palomera, FernandoÁlvarez Domingo, MercedesSíntesi orgànicaAntibiòticsProductes naturalsPèptidsOrganic synthesisAntibioticsNatural productsPeptidesThiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential.MDPIUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/57126engcc-by (c) Just Baringo, Xavier et al., 2014info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2404322017-05-23T04:56:02Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/240432Repeated doses of methylone, a new drug of abuse, induce changes in serotonin and dopamine systems in the mouseLópez-Arnau, RaúlMartínez-Clemente, JoséAbad, SoniaPubill Sánchez, DavidCamarasa García, JordiEscubedo Rafa, ElenaDroguesEfectes fisiològicsNeurotoxicologiaEscorça cerebralLòbul frontalHipocamp (Cervell)Drugs of abusePhysiological effectNeurotoxicologyCerebral cortexFrontal lobeHippocampus (Brain)Rationale Methylone, a new drug of abuse sold as"bath salts' has similar effects to ecstasy or cocaine. Objective We have investigated changes in dopaminergic and serotoninergic markers, indicative of neuronal damage, induced by methylone in the frontal cortex, hippocampus and striatum of mice and according two different treatment schedules. Methods Methylone was given subcutaneously to male Swiss CD1 mice and at an ambient temperature of 26ºC. Treatment A: three doses of 25 mg/Kg at 3.5 h interval between doses for two consecutive days. Treatment B: four doses of 25 mg/Kg at 3 h interval in one day. Results Repeated methylone administration induced hyperthermia and a significant loss in body weight. Following treatment A, methylone induced transient dopaminergic (frontal cortex) and serotoninergic (hippocampus) impairment. Following treatment B, transient dopaminergic (frontal cortex) and serotonergic (frontal cortex and hippocampus) changes 7 days after treatment were found. We found evidence of astrogliosis in the CA1 and the dentate gyrus of the hippocampus following treatment B. The animals also showed an increase in immobility time in the forced swim test, pointing to a depressive-like behavior. In cultured cortical neurons, methylone (for 24 and 48 h) did not induce a remarkable cytotoxic effect. Conclusions The neural effects of methylone differ depending upon the treatment schedule. Neurochemical changes elicited by methylone are apparent when administered at an elevated ambient temperature, four times per day at 3 h intervals, which is in accordance with its short half-life.Springer VerlagUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/58167eng(c) Springer Verlag, 2014info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2438882017-05-23T04:56:07Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/243888Unsaturated Oxazolopiperidone Lactams: an Unexpected Domino-type Double Conjugate Addition<br>cyclization ProcessAmat Tusón, MercedesLlor Brunés, NúriaCheca Castaño, BegoñaPérez Bosch, MariaBosch Cartes, JoanCompostos heterocíclicsLactamesSíntesi asimètricaHeterocyclic compoundsLactamsAsymmetric synthesisReactions of 2-acetylindole enolate with unsaturated oxazolopiperidones 3, 4 and 10 unexpectedly gives pentacyclic dilactams 6, 7 and 11, respectively, resulting from a domino-type process involving two successive conjugate additions and a final cyclization.Michigan PublishingUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/61084engcc-by-nc (c) Amat Tusón, Mercedes et al., 2014info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc/3.0/es">http://creativecommons.org/licenses/by-nc/3.0/es</a>
oai:recercat.cat:2072/2104322017-05-23T04:56:12Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/210432Model studies on the synthesis of madangamine alkaloids. Assembly of the macrocyclic ringsProto, StefanoAmat Tusón, MercedesPérez Bosch, MariaBallette, RobertoRomagnoli, FedericaMancinelli, AndreaBosch Cartes, JoanAlcaloidesModels molecularsCompostos heterocíclicsProcessos químicsAlkaloidsMolecular modelsHeterocyclic compoundsChemical processesUsing simplified model derivatives, the assembly of the macrocyclic rings of madangamines, including the 13- and 14-membered D rings of madangamines C-E, the all-cis-triunsaturated 15-membered D ring of madangamine A, and the (Z,Z)-unsaturated 11-membered E ring common to madangamines A-E, has been studied.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/34544eng(c) American Chemical Society , 2012info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2459212017-05-23T04:56:14Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/245921Simple sugar intake and hepatocellular carcinoma: epidemiological and mechanistic insightLaguna Egea, Juan CarlosAlegret i Jordà, MartaRoglans i Ribas, NúriaFructosaMalalties del fetgeCàncer de fetgeObesitatResistència a la insulinaFructoseLiver diseasesLiver cancerObesityInsulin resistanceSugar intake has dramatically increased during the last few decades. Specifically, there has been a clear trend towards higher consumption of fructose and high fructose corn syrup, which are the most common added sugars in processed food, soft drinks and other sweetened beverages. Although still controversial, this rising trend in simple sugar consumption has been positively associated with weight gain and obesity, insulin resistance and type 2 diabetes mellitus and non-alcoholic fatty liver disease. Interestingly, all of these metabolic alterations have also been related to the development of hepatocellular carcinoma. The purpose of this review is to discuss the evidence coming from epidemiological studies and data from animal models relating the consumption of simple sugars, and specifically fructose, with an increased risk of hepatocellular carcinoma and to gain insight into the putative molecular mechanisms involved.MDPIUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/62165engcc-by (c) Laguna Egea, Juan Carlos et al., 2014info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2500532017-05-23T04:56:20Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/2500533,4-Methylenedioxymethamphetamine enhances kainic acid convulsive susceptibilityAbad, SoniaJunyent Herena, FèlixAuladell i Costa, M. CarmePubill Sánchez, DavidPallàs i Llibería, Mercè, 1964-Camarasa García, JordiEscubedo Rafa, ElenaCamins Espuny, AntoniAl·lucinògensAmfetaminesCompostos heterocíclicsEpilèpsiaNeurotoxicologiaRatolins (Animals de laboratori)Sistema nerviós centralHallucinogenic drugsAmphetaminesHeterocyclic compoundsEpilepsyNeurotoxicologyMice (Laboratory animals)Central nervous systemAbstract Kainic acid (KA) causes seizures and neuronal loss in the hippocampus. The present study investigated whether a recreational schedule of 3,4-methylenedioxymethamphetamine (MDMA) favours the development of a seizure state in a model of KA-induced epilepsy and potentiates the toxicity profile of KA (20 or 30 mg/kg). Adolescent male C57BL/6 mice received saline or MDMA t.i.d. (s.c. every 3 h), on 1 day a week, for 4 consecutive weeks. Twenty-four hours after the last MDMA exposure, the animals were injected with saline or KA (20 or 30 mg/kg). After this injection, we evaluated seizures, hippocampal neuronal cell death, microgliosis, astrogliosis, and calcium binding proteins. MDMA pretreatment, by itself, did not induce neuronal damage but increased seizure susceptibility in all KA treatments and potentiated the presence of Fluoro-Jade-positive cells in CA1. Furthermore, MDMA, like KA, significantly decreased parvalbumin levels in CA1 and dentate gyrus, where it potentiated the effects of KA. The amphetamine derivative also promoted a transient decrease in calbindin and calretinin levels, indicative of an abnormal neuronal discharge. In addition, treatment of cortical neurons with MDMA (10<br>50 μM) for 6 or 48 h significantly increased basal Ca2 +, reduced basal Na+ levels and potentiated kainate response. These results indicate that MDMA potentiates KA-induced neurodegeneration and also increases KA seizure susceptibility. The mechanism proposed includes changes in Calcium Binding Proteins expression, probably due to the disruption of intracellular ionic homeostasis, or/and an indirect effect through glutamate release.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/65528eng(c) Elsevier B.V., 2014info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2500542017-05-23T04:56:21Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/250054Serotonergic impairment and memory deficits in adolescent rats after binge exposure of methyloneLópez Arnau, RaúlMartínez-Clemente, J.Pubill Sánchez, DavidEscubedo Rafa, ElenaCamarasa García, JordiAmfetaminesNeurotoxicologiaSistema nerviós centralHipocamp (Cervell)Lòbul frontalRates (Animals de laboratori)Trastorns de la memòriaAmphetaminesNeurotoxicologyCentral nervous systemHippocampus (Brain)Frontal lobeRats as laboratory animalsMemory disordersMethylone is a cathinone derivative that has recently emerged as a designer drug of abuse in Europe and the USA. Studies on the acute and long-term neurotoxicity of cathinones are starting to be conducted. We investigated the neurochemical/enzymatic changes indicative of neurotoxicity after methylone administration (4 × 20 mg/kg, subcutaneously, per day with 3 h intervals) to adolescent rats, to model human recreational use. In addition, we studied the effect of methylone on spatial learning ad memory using the Morris water maze paradigm. Our experiments were carried out at a high ambient temperature to simulate the hot conditions found in dance clubs where the drug is consumed. We observed a hyperthermic response to methylone that reached a peak 30 min after each dose. We determined a serotonergic impairment in methylone-treated rats, especially in the frontal cortex, where it was accompanied by astrogliosis. Some serotonergic alterations were also present in the hippocampus and striatum. No significant neurotoxic effect on the dopaminergic system was identified. Methylone-treated animals only displayed impairments in the probe trial of the Morris water maze, which concerns reference memory, while the spatial learning process seemed to be preserved.Sage PublicationsUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/65530eng(c) López Arnau, Raúl et al., 2014info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2506552017-05-23T04:56:23Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/250655Multigram synthesis and in vivo efficacy studies of a novel multitarget anti-Alzheimer's compoundSola, IreneViayna, ElisabetGómez Nadal, TàniaGaldeano Cantador, CarlosCassina, MatteoCamps García, PelayoRomeo, MargheritaDiomede, LuisaSalmona, MarioFranco, PilarSchaeffer, MireilleColantuono, DiegoRobin, DavidBrunner, DanielaTaub, NicoleHutter-Paier, BirgitMuñoz-Torrero López-Ibarra, DiegoMalaltia d'AlzheimerDisseny de medicamentsQuímica farmacèuticaDianes farmacològiquesRatolins (Animals de laboratori)Alzheimer's diseaseDrug designPharmaceutical chemistryDrug targetingMice (Laboratory animals)We describe the multigram synthesis and in vivo efficacy studies of a donepezil‒huprine hybrid that has been found to display a promising in vitro multitarget profile of interest for the treatment of Alzheimer's disease (AD). Its synthesis features as the key step a novel multigram preparative chromatographic resolution of intermediate racemic huprine Y by chiral HPLC. Administration of this compound to transgenic CL4176 and CL2006 Caenorhabditis elegans strains expressing human Aβ42, here used as simplified animal models of AD, led to a significant protection from the toxicity induced by Aβ42. However, this protective effect was not accompanied, in CL2006 worms, by a reduction of amyloid deposits. Oral administration for 3 months to transgenic APPSL mice, a well-established animal model of AD, improved short-term memory, but did not alter brain levels of Aβ peptides nor cortical and hippocampal amyloid plaque load. Despite the clear protective and cognitive effects of AVCRI104P4, the lack of Aβ lowering effect in vivo might be related to its lower in vitro potency toward Aβ aggregation and formation as compared with its higher anticholinesterase activities. Further lead optimization in this series should thus focus on improving the anti-amyloid/anticholinesterase activity ratio.MDPIUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/65727engcc-by (c) Sola, Irene et al., 2015info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2099672017-05-23T04:56:28Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/209967An enantioselective entry to cis-perhydroisoquinolinesAmat Tusón, MercedesPérez Bosch, MariaMinaglia, Annamaria TaniaCasamitjana i Badia, NúriaBosch Cartes, JoanIsoquinolinaIsoquinolineAn enantioselective route to cis-perhydroisoquinolines, involving a cyclocondensation reaction of (R)-phenylglycinol with a racemic oxoester, a stereoselective conjugate addition to an unsaturated bicyclic lactam, and the closure of the carbocyclic ring by a ring-closing metathesis as the key steps is reported. This route allows the preparation of 3-cyano derivatives as well as cis-octahydroisoquinolines bearing a quaternary center at the C4-position.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/34586eng(c) American Chemical Society , 2005info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2574142017-05-23T04:56:30Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/257414Serotonin is involved in the psychostimulant and hypothermic effect of 4-methylamphetamine in rats.Rubio, MarLópez Arnau, RaúlPubill Sánchez, DavidEscubedo Rafa, ElenaCamarasa García, JordiAmfetaminesFarmacologiaHipotèrmiaSistema nerviós centralSerotoninaAmphetaminesPharmacologyHypothermiaCentral nervous systemSerotonin4-Methylamphetamine (4-MA) has recently emerged as a designer drug of abuse in Europe and it is consumed always with amphetamine. There have been reported some deaths and non-fatal intoxications related to 4-MA. We investigated the changes in locomotor activity and body temperature after 4-MA administration to male Sprague-Dawley rats. Our experiments were carried out at a normal or high ambient temperature. 4-MA (2.5-10 mg/Kg, given subcutaneously) increased, in a dose-dependent manner, the horizontal locomotor activity that was significantly reduced by ketanserin, p-cholorophenylalanine (pCPA) or haloperidol, but not by pindolol. In addition, we have studied the effect of 4-MA on core body temperature by means of an implanted electronic thermograph, enabling continuous measurement of body temperature. We observed a dose-dependent hypothermic response to 4-MA that reached a maximum 45 min after a single injection. We also evidenced slight tachyphylaxis to the hypothermic effect when 4-MA was administered four times in a 2 h interval. The pre-treatment of animals with pCPA or pindolol, but not with ketanserin, fully abolished the hypothermic effect of 4-MA. With all that, we conclude that hypothermia induced by 4-MA is due to the release of 5-HT which activates postsynaptic 5-HT1A receptors.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/68592eng(c) Elsevier B.V., 2015info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2582882017-05-23T04:56:32Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/258288Amino acid-protecting groupsIsidro Llobet, AlbertÁlvarez Domingo, MercedesAlbericio Palomera, FernandoAminoàcidsQuímica orgànicaAminesÀcids carboxílicsSulfursPèptidsAmino acidsOrganic chemistryAminesCarboxylic acidsSulfidesPeptidesSynthetic organic chemistry is based on the concourse of reagents and catalysts to achieve the clean formation of new bonds and appropriate protecting groups are required to prevent the formation of undesired bonds and side-reactions. Thus a promising synthetic strategy can be jeopardized if the corresponding protecting groups are not properly chosen.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/69570eng(c) American Chemical Society , 2009info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2603002017-05-23T04:56:33Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/260300A strategy for the triarylation of pyrrolopyrimidines by using microwave-promoted cross-coupling reactionsPrieur, VanessaPujol Dilmé, M. DolorsGuillaumet, GéraldCompostos heterocíclicsNitrogenQuímica orgànicaReaccions químiquesHeterocyclic compoundsNitrogenOrganic chemistryChemical reactionsNew pyrrolo[2,3-d]pyrimidines that have aryl groups at the 2-, 4-, and 6-positions were prepared by the arylation reaction of 4-chloro-7-methyl-2-(methylthio)-6-phenylpyrrolo[2,3-d]pyrimidine (6) and the corresponding arylboronic acid under Suzuki-Miyaura conditions followed by a second arylation under Liebeskind-Srogl cross-coupling conditions. A parallel study that began with the C-2 chemoselective arylation of 6 under Liebeskind-Srogl conditions followed by a Suzuki-Miyaura coupling at C-4 was carried out, and the results of each route were compared. All of the tranformations were performed under microwave irradiation.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/96646eng(c) Wiley-VCH, 2015info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2603722017-05-23T04:56:36Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/260372Synthesis of cinacalcet: an enantiopure active pharmaceutical ingredient (API)Barniol-Xicota, MartaLeiva Martínez, RosanaEscolano Mirón, CarmenVázquez Cruz, SantiagoAmidesAminesMedicamentsAmidesAminesDrugsCinacalcet hydrochloride is the only approved drug acting as calcimimetic, a new class of compds. used in the therapy of secondary hyperparathyroidism and parathyroid carcinoma. Several generic drug manufacturers and research groups from academia have reported alternative approaches to this mol., mainly from (R)-(+)-1-(1-naphthyl)ethylamine. There are mainly three strategies that have been used to couple this readily accessible enantiopure amine to the other part of the mol.: amide formation followed by redn., reaction with an aldehyde and redn. of the resulting imine, and nucleophilic substitution with a suitable partner that carries a leaving group. More exotic approaches have also been disclosed. In the present review all of them are discussed. 1 Introduction 2 Synthetic Approaches Involving the Synthesis of an Amide Followed by Its Redn. 2.1 Approaches Involving Satd. Amide 2 from Acid 32.2 Approaches Involving Acrylamide 52.3 Alternatives Approaches Involving Amides 3 Synthetic Approaches Involving a Reductive Amination 3.1 Processes for the Synthesis of 3-(Trifluoromethyl)cinnamaldehyde (18) and 3-[3-(Trifluoromethyl)phenyl]propanal (20) 3.2 Processes Involving 183.3 Processes Involving 204 Synthetic Approaches Involving a Substitution Reaction 4.1 Substitutions Involving Alkyl Halides or Pseudohalides 4.2 Substitutions Involving Allyl Halides or Pseudohalides 4.3 Substitution Involving a Propynyl Mesylate 4.4 Direct Substitution without Activating the Hydroxyl Group 5 Misc. Synthetic Approaches 6 Conclusions.Universidad Nacional de La PlataUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/96772engcc-by-nc-nd (c) Barniol-Xicota, Marta et al., 2016info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc-nd/3.0/es">http://creativecommons.org/licenses/by-nc-nd/3.0/es</a>
oai:recercat.cat:2072/2103782017-05-23T04:56:40Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/210378An enantioselective synthetic route to cis-2,4-disubstituted and 2,4-bridged piperidinesAmat Tusón, MercedesPérez Bosch, MariaMinaglia, Annamaria T.Bosch Cartes, JoanCompostos organometàl·licsCoureSíntesi orgànicaLactamesOrganometallic compoundsCopperSynthetic organic chemistryLactamsA synthetic route to enantiopure cis-2,4-disubstituted and 2,4-bridged piperidines is reported, the key step being a stereoselective conjugate addition of an organocuprate to a phenylglycinol-derived unsaturated lactam bearing a substituent at the 8a-position.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/36346eng(c) American Chemical Society , 2008info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2621922017-05-23T04:56:42Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/262192A general method for the synthesis of enantiopure 1,5-amino alcoholsGuignard, GuillaumeLlor Brunés, NúriaUrbina Teixidor, AinaBosch Cartes, JoanAmat Tusón, MercedesSíntesi orgànicaSíntesi asimètricaReducció químicaLactamesOrganic synthesisAsymmetric synthesisReduction (Chemistry)LactamsA variety of (R)-phenylglycinol-derived oxazolopiperidone lactams 1-14 were converted to linear-chain enantiopure amino diols 15-26 by reduction with LiNH2BH3 in an unprecedented process involving the simultaneous reductive opening of the oxazolidine and lactam rings. Subsequent removal of the phenylethanol moiety gave enantiopure 5-amino-1-pentanols bearing substituents at the 2-, 3-, 4-, 2,2-, 2,3- 2,4- and 3,4-positions (28-36), which were isolated as their N-Boc derivatives.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/98971eng(c) Wiley-VCH, 2016info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2623762017-05-23T04:56:45Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/262376Enantio- and Diastereoconvergent Cyclocondensation Reactions: Synthesis of Enantiopure cis-Decahydroquinolines.Amat Tusón, MercedesGhirardi, ElenaNavio, LauraGriera Farres, RosaLlor Brunés, NúriaMolins i Grau, EliesBosch Cartes, JoanQuímica orgànicaAlcaloidesSíntesi asimètricaLactamesCompostos heterocíclicsOrganic chemistryAlkaloidsAsymmetric synthesisLactamsHeterocyclic compoundsUp to four stereocenters with a well-defined configuration are generated in a single synthetic step by the cyclocondensation of (R)-phenylglycinol or (1S,2R)-1-amino-2-indanol with stereoisomeric mixtures (racemates, meso forms, diastereoisomers) of cyclohexanone-based δ-keto-acid and δ-keto-diacid derivatives in enantio- and diastereoconvergent processes that involve dynamic kinetic resolution and/or desymmetrization of enantiotopic groups. A detailed analysis of the stereochemical outcome of this process is presented. This method provides easy access to enantiopure 8- and 6,8-substituted cis-decahydroquinolines, including alkaloids of the myrioxazine family.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/99269eng(c) Wiley-VCH, 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2702192017-05-23T04:56:48Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/270219Synthesis of fluvirucins and their aglycons, the fluvirucininsAmat Tusón, MercedesLlor Brunés, NúriaGuignard, GuillaumeBosch Cartes, JoanLactamesGlucòsidsLactamsGlucosidesFluvirucins are bioactive macrolactam glycosides isolated from actinomycetes. This review gives an overview of this family of natural products, covering isolation, biological activities, biosynthesis, and total synthesis. The synthesis of fluvirucins and their aglycons, the fluvirucinins, is presented, paying special attention to the synthetic strategy and stereochemical aspects. 1 Introduction 2 Isolation, Biological Activity, and Biosynthesis 3 Synthetic Approaches 3.1 Closure of the 14-Membered Ring by Ring-Closing Metathesis 3.2 Closure of the 14-Membered Ring by Macrolactamization 3.3 Construction of the 14-Membered Ring by Aza-Claisen Ring Expansion 4 ConclusionUniversidad Nacional de La PlataUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/104863engcc-by-nc-nd (c) Amat Tusón, Mercedes et al., 2016info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc-nd/3.0/es">http://creativecommons.org/licenses/by-nc-nd/3.0/es</a>
oai:recercat.cat:2072/2105552017-05-23T04:56:50Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/210555Enantioselective formal synthesis of ent-rhynchophylline and ent-isorhynchophyllineAmat Tusón, MercedesRamos, CarlosPérez Bosch, MariaMolins i Grau, EliesFlorindo, PedroSantos, Maria M. M.Bosch Cartes, JoanAlcaloidesSíntesi asimètricaEstereoquímicaAlkaloidsAsymmetric synthesisStereochemistryStarting from (S)-tryptophanol, a formal synthesis of ent-rhyncho-phylline and ent-isorhynchophylline, involving stereoselective cyclocondensation, spirocyclization, and alkylation reactions, and the final adjustment of the oxidation level at the oxindole and piperidine moieties, is reported.Royal Society of ChemistryUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/36425eng(c) Amat Tusón, Mercedes et al., 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2812162017-05-23T04:56:53Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/281216Stereoselective syntheses of the antihistaminic drug olopatadine and its E-isomerBosch Cartes, JoanBachs, JordiGómez, Antonia M.Griera Farres, RosaÉcija, MartaAmat Tusón, MercedesAntihistamínicsEstructura molecularSíntesi orgànicaAntihistaminesMolecular structureOrganic synthesisPractical stereoselective synthetic routes to the antihistaminic drug olopatadine and its E-isomer have been developed, the key steps being a trans stereoselective Wittig olefination using a nonstabilized phosphorus ylide and a stereoselective Heck cyclization. The stereoselectivity of the Wittig reaction depends on both the phosphonium salt anion and the cation present in the base used to generate the ylide.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/107829eng(c) American Chemical Society , 2012info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2812952017-05-23T04:56:54Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/281295A Biomimetic Enantioselective Approach to the Decahydroquinoline Class of Dendrobatid AlkaloidsAmat Tusón, MercedesGriera Farres, RosaFabregat, RobertMolins, EliesBosch Cartes, JoanAlcaloidesAmfibisBiomimèticaAlkaloidsAmphibiansBiomimeticsFrogs of the neotropical family Dendrobatidae produce a remarkably diverse array of biologically active alkaloids. One of the major classes of these amphibian alkaloids[1] are the decahydroquinolines, which have been isolated not only from skin extracts of dendrobatid and mantelline frogs,[2] but also from bufonid toads,[3] tunicates,[4] marine flatworms,[4b] and myrmicine ants.[5] They possess either a cis or trans decahydroquinoline ring fusion, with a side-chain substituent at both the C2 and C5 positions and, in the lepadin series,[4] an acylated hydroxy group at the C3 position. The most representative decahydroquinoline alkaloid is cis-195A (formerly called pumiliotoxin C), first isolated in 1969 from a Panamanian population of Dendrobates pumilio. [6] The source of amphibian alkaloids remains an unresolved and challenging question,[1] in particular after the discovery that some of these alkaloids also occur in ants, thus strengthening a dietary hypothesis for their origin in frogs.[5] Although there are no conclusive studies concerning the biosynthesis of these toxins and, consequently, little is known about the biosynthetic pathways, there has been speculation as to possible derivation from the polyketide route by aminocyclization of polycarbonyl intermediates (A), leading to either 2,5-disubstituted decahydroquinolines (C) or spiropiperidines (histrionicotoxins).[1a,b, 7] In accordance with this hypothesis, a plausible biosynthetic pathway to the decahydroquinoline class of dendrobatid alkaloids is depicted inWiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/108023eng(c) Wiley-VCH, 2008info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2812962017-05-23T04:56:55Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/281296Enantioselective synthesis of lepadins A D from a phenylglycinol-derived hydroquinolone lactamAmat Tusón, MercedesPinto, AlexandreGriera Farres, RosaBosch Cartes, JoanAlcaloidesLactamesCompostos heterocíclicsSíntesi asimètricaAlkaloidsLactamsHeterocyclic compoundsAsymmetric synthesisThe marine alkaloids (-)-lepadins A-C and (+)-lepadin D, belonging to two diastereoisomeric series, were synthesized from an (R)-phenylglycinol-derived tricyclic lactam via a common cis-decahydroquinoline intermediate. Crucial aspects of the synthesis are the stereochemical control in the assembly of the cis-decahydroquinoline platform, in the introduction of the C2 methyl and C3 hydroxy substituents, and in the generation of the C5 stereocenter.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/108026eng(c) Wiley-VCH, 2015info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2812972017-05-23T04:56:55Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/281297Stereoselectivesynthesis of (-)-lepadins A-CAmat Tusón, MercedesPinto, AlexandreGriera Farres, RosaBosch Cartes, JoanAlcaloidesLactamesFarmacologiaAlkaloidsLactamsPharmacologyA concise synthesis of the marine alkaloids ()-lepadins A-C from a phenylglycinol-derived tricyclic lactam is reported. Key steps from the stereochemical standpoint involve stereoselective cyclocondensation, double bond hydrogenation, oxazolidine opening, hydroboration- oxidation, and Horner-Wadsworth-Emmons reactions.Royal Society of ChemistryUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/108043eng(c) Amat Tusón, Mercedes et al., 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2812982017-05-23T04:56:56Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/281298Stereocontrolled access to enantiopure to enantiopure 7-substituted cis- and trans-octahydroindolesGhirardi, ElenaGriera Farres, RosaPiccichè, MiriamMolins i Grau, EliesFernández Cadenas, IsraelBosch Cartes, JoanAmat Tusón, MercedesLactamesSíntesi asimètricaLactamsAsymmetric synthesisCyclocondensation of (R)-phenylglycinol with stereoisomeric mixtures (racemates, cis/trans) of 3-substituted 2- oxocyclohexaneacetates stereoselectively afforded tricyclic oxazoloindolone lactams, from which straightforward procedures for the stereocontrolled formation of enantiopure 7-substituted octahydroindoles with a variety of stereochemical patterns have been developed. The methodology has been successfully applied to the synthesis of (+)-α-lycorane.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/108046eng(c) American Chemical Society , 2016info:eu-repo/semantics/embargoedAccess
oai:recercat.cat:2072/2855522017-05-23T04:56:58Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/285552Preparation and Double Michael Addition Reactions of a Synthetic Equivalent of Nazarov ReagentAmat Tusón, MercedesArioli, FedericaPérez Bosch, MariaMolins i Grau, EliesBosch Cartes, JoanIndicadors (Química)Proves i reactius químicsLactamesIndicators and test-papersChemical tests and reagentsLactamsA synthetic equivalent of the Nazarov reagent, the silyl derivative 2, able to undergo base-catalyzed double Michael addition reactions with a,b-unsaturated carbonyl compounds, has been developed. The new reagent satisfactorily reacts with unsaturated indolo[2,3-a]quinolizidine lactams to give pentacyclic yohimbinone-type derivatives.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/108108eng(c) American Chemical Society , 2013info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2859092017-06-06T01:43:22Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/285909Modificacions en la unió de la glipentida a components hemàtics per efecte d'altres medicamentsLópez, R.Rimbau i Barreras, VíctorTorralba Rodríguez, AntonioHematologiaFarmacologiaEfectes secundaris dels medicamentsBiocompatibilitatAlbúminesHematologyPharmacologyDrug side effectsBiocompatibilityAlbuminsÉs evident que la unió d'un medicament a les estructures proteiques deis receptors té una gran importància per a l'activitat farmacològica del producte. Nogensmenys, cal no oblidar que les interaccions medicament-proteïna poden tenir lloc amb un gran nombre de proteïnes, cosa que regula l'absorció, distribució, metabolisme i excreció del medicament. ...Acadèmia de Ciències Mèdiques i de la Salut de Catalunya i de BalearsUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/111604cat(c) López, R. et al., 1980info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2859102017-06-06T01:43:30Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/285910Access to Enantiopure 5‑, 7‑, and 5,7-Substituted cis- Decahydroquinolines: Enantioselective Synthesis of (−)-Cermizine BPinto, AlexandreGriera Farres, RosaMolins i Grau, EliesFernández Cadenas, IsraelBosch Cartes, JoanAmat Tusón, MercedesAlcaloidesLactamesAlkaloidsLactamsStereoconvergent cyclocondensation reactions of (R)- or (S)-phenylglycinol with appropriately substituted cyclohexanone-based δ-keto esters are the key steps of short synthetic routes to enantiopure 5-, 7-, and 5,7-substituted cisdecahydroquinolines. The factors governing the stereoselectivity of the cyclocondensation are discussed. The potential of the methodology is illustrated by a protecting-group-free synthesis of the phlegmarine-type Lycopodium alkaloid (-)-cermizine B.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/111625eng(c) American Chemical Society , 2017info:eu-repo/semantics/embargoedAccess
oai:recercat.cat:2072/2459202017-07-18T08:02:45Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/245920Rcor2 underexpression in senescent mice: a target for inflammaging?Alvarez-López, Maria J.Molina Martínez, PatriciaCastro-Freire, MarcoCosín Tomàs, MartaCristòfol i Martínez, Rosa M.Párrizas, MarcelinaEscorihuela, Rosa M.Pallàs i Llibería, Mercè, 1964-Sanfeliu i Pujol, CoralKaliman, PerlaEnvellimentInflamacióGensCromatinaInterleucinesAgingInflammationGenesChromatinInterleukinsBACKGROUND: Aging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program. METHODS: To assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro. RESULTS: P8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes. CONCLUSIONS: Data presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammagingBioMed CentralUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/62163engcc-by (c) Alvarez-López, Maria J. et al., 2014info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2900262017-07-18T08:02:47Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/290026Algunes notes sobre la producció científica empordanesaVallès Xirau, Joan, 1959-Cañigueral i Folcarà, SalvadorHistòria de la ciènciaEmpordà (Catalunya)History of sciencesEmpordà (Catalonia)Quan hom intenta de fer una valoració d'allò que ha estat o és la producció cultural en un determinat àmbit geogràfic, és del tot pertinent -i necessari- de dedicar un espai a una faceta d'aquest afer que ben sovint és objecte d'oblit: la ciència. Que l'Emporda és terra d'artistes i literats emèrits és cosa sabuda. I ha estat tanta la fama adquirida, merescudament sens dubte, per alguns d'aquests, que molla gent, en pensar en la nostra terra en l'aspecte cultural, només al·ludeix a ells...Universitat de BarcelonaUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/113651cat(c) Vallès Xirau, Joan, 1959- et al., 1986info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2907312017-07-19T22:36:31Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/290731Asymmetric synthesis of octahydroindoles via a domino robinson annulation/5-endo intramolecular aza-michael reactionParra Montes, ClaudioBosch, CarolineGómez-Bengoa, EnriqueBonjoch i Sesé, JosepBradshaw, BenQuímica orgànicaSíntesi orgànicaAlcaloidesOrganic chemistryOrganic synthesisAlkaloidsA straightforward two-step asymmetric synthesis of octahydroindoles has been developed based on two complimentary strategies: (i) an organocatalyzed Michael reaction followed by a tandem Robinson-aza-Michael double cyclization catalyzed by PS-BEMP; (ii) a diastereoselective cyclization, which formally constitutes a remote 1,6 asymmetric induction mediated by PS-BEMP. This allowed the construction of complex octahydroindoles with up to 4 stereocenters, excellent enantioselectivities (up to 95% ee) and complete diastereoselective control in a single pot operation. DFT calculations were performed to understand the origin of this effect.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/114102eng(c) American Chemical Society , 2016info:eu-repo/semantics/embargoedAccess
oai:recercat.cat:2072/2900252017-09-18T05:34:42Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/290025Suspended planar-array chips for molecular multiplexing at the microscaleTorras, NúriaAgusil Antonoff, Juan PabloVázquez, PatriciaDuch, MartaHernández-Pinto, Alberto M.Samitier i Martí, JosepRosa, Enrique J. de laEsteve, JaumeSuárez, TeresaPérez García, M. Lluïsa (Maria Lluïsa)Plaza, José A.PolímersSuspensions (Química)MultiplexatgeCèl·lules epitelialsPolymersSuspensions (Chemistry)MultiplexingEpithelial cellsA novel suspended planar-array chips technology is described, which effectively allows molecular multiplexing using a single suspended chip to analyze extraordinarily small volumes. The suspended chips are fabricated by combining silicon-based technology and polymer-pen lithography, obtaining increased molecular pattern flexibility, and improving miniaturization and parallel production. The chip miniaturization is so dramatic that it permits the intracellular analysis of living cells.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/112380engcc-by-nc-nd (c) Torras, Núria et al., 2016info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc-nd/3.0/es">http://creativecommons.org/licenses/by-nc-nd/3.0/es</a>
oai:recercat.cat:2072/2900272017-10-06T05:29:58Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/290027Radiofarmàcia: una nova especialitatSoriano, B.Rimbau i Barreras, VíctorRadiofàrmacsSubstàncies radioactivesRadiologia mèdicaFarmacèuticsRadiopharmaceuticalsRadioactive substancesMedical radiologyPharmacistsDes del seu descobriment fins als nostres dies,la utilització de la radioactivitat per l'home no ha parat d'augmentar quantitativament i qualitativa. D'aquesta manera, deixant de banda els aspectes bèl·lics, l'ús de les tècniques radioactives ha esdevingut una cosa freqüent, i sovint imprescindible, en camps tan allunyats com poden ser els processos productius de les indústries papereres o metal·lúrgiques i els de la recerca en les ciències biològiques i de la salut.Acadèmia de Ciències Mèdiques i de la Salut de Catalunya i de BalearsUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/113722cat(c) Soriano, B. et al., 1986info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2930132017-10-07T05:29:43Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/293013La ingesta materna de fructosa líquida acentúa la dislipemia que origina el consumo de fructosa en la descendencia de hembra adultaRodríguez, LourdesPanadero, María I.Rodrigo, SilviaRoglans i Ribas, NúriaOtero, PaolaÁlvarez-Millán, Juan J.Laguna Egea, Juan CarlosBocos, CarlosGenètica mèdicaFructosaNutrició en l'embaràsLípids de la sangMedical geneticsFructoseNutrition in pregnancyBlood lipidsEl consumo de bebidas edulcoradas ricas en fructosa ha aumentado de forma considerable en las últimas décadas, de forma paralela a la mayor incidencia de enfermedades tales como la diabetes, la obesidad y las enfermedades cardiovasculares...Medigene PressUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/116245spacc-by (c) Rodríguez, Lourdes et al., 2016info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3023192017-12-07T06:30:37Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/302319Alternative access to functionalized 2,8-ethanonoradamantane derivativesCamps García, PelayoGómez Nadal, TàniaOtermin Esteras, AneFont Bardia, Ma. MercedesSíntesi orgànicaCompostos policíclicsDifracció de raigs XOrganic synthesisPolycyclic compoundsX-rays diffraction7a-(Methoxycarbonyl)-N-methyl-1,3a,5,6,7,7a-hexahydro-4H-1,4,6-(epiethane[1,1,2]triyl) indene-4,9-dicarboximide has been prepared through a modification of a previous synthetic sequence, in which the benzyloxymethyl hydroxyl protecting group has been replaced by methoxymethyl, to avoid the apparent formation of a benzyl ester derivative as a side product. The overall yield of the new synthetic sequence is comparable to the previous one. Two advantages of the new procedure are: (a) no benzyl ester was formed and (b) a stereoisomeric mixture of syn- and anti-alcohols at the beginning of the synthetic sequence could be separated and the rest of the synthesis could be carried out with the main syn-stereoisomer instead of the corresponding stereoisomeric mixture as it was the case in the previous process.MDPIUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/118465engcc-by (c) Camps García, Pelayo et al., 2017info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2816082017-12-13T06:31:18Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/281608Sudemycin K: a synthetic anti-tumor splicing inhibitor variant with improved activity and versatile chemistryMakowski, KamilVigevani, LuisaAlbericio Palomera, FernandoValcárcel, JuanÁlvarez Domingo, MercedesCàncerMedicamentsInhibidors enzimàticsCancerDrugsEnzyme inhibitorsImportant links exist between the process of pre-mRNA splicing and cancer, as illustrated by the frequent mutation of splicing factors in tumors and the emergence of various families of antitumor drugs that target components of the splicing machinery, notably SF3B1, a protein subunit of spliceosomal U2 small nuclear ribonucleoprotein particle (snRNP). Sudemycins are synthetic compounds that harbor a pharmacophore common to various classes of splicing inhibitors. Here, we describe the synthesis and functional characterization of novel sudemycin analogues that function- ally probe key functional groups within this pharmacophore. Our results confirm the importance of a conjugated diene group and in addition reveal significant spatial flexibility in this region of the molecule. Sudemycin K, a derivative that replaces the pharmacophore's oxycarbonyl by an amide group, displays improved potency as an inhibitor of cancer cell proliferation, as a regulator of alternative splicing in cultured cells and as an inhibitor of in vitro spliceosome assembly. Sudemycin K displays higher stability, likely related to the replacement of the oxycarbonyl group, which can be a substrate of esterases, by an amide group. The activity and special reactivity of sudemycin K can pave the way to the synthesis and evaluation of a variety of novel sudemycin derivatives.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/108186eng(c) American Chemical Society, 2016info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/2621562018-02-07T06:32:15Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/262156Pasaporte a la profesión en el Grado de FarmaciaEscolano Mirón, CarmenGarcía Montoya, EncarnaPallàs i Llibería, Mercè, 1964-Vázquez Cruz, SantiagoMiñarro Carmona, MontserratMarqués Villavecchia, Ana M.Lluch Guasch, AnnaFarmàciaTítols acadèmicsInnovacions educativesPràcticumsPharmacyAcademic degreesEducational innovationsPracticumsEspai Europeu d'Educació SuperiorLa incorporació del sistema universitari espanyol al Espai Europeu d’Educació Superior (EEES) ha implicat una sèrie d’adaptacions dels graus. Entre aquests s’ha de destacar un període de pràctiques externes a la pròpia universitat, lo que ha comportar una sèrie de canvis considerables en els plans d’estudis de manera que s’aconsegueixi un balanç més equilibrat entre la formació teòrica i pràctica rebuda pels estudiants. Aquest nou marc de treball ha estat confirmat legalment pel Govern espanyol (Real Decreto 1393/2007, de 20 d’octubre i Real Decreto 1707/2011 de 18 de novembre) i en el cas de la Universitat de Barcelona amb la publicació d’una normativa de pràctiques (Normativa de pràctiques acadèmiques externes dels estudiants de la Universitat de Barcelona).
Aprofitant aquesta oportunitat per adaptar el Grau de Farmàcia a la realitat social actual, l’equip deganal de la Facultat de Farmàcia amb el recolzament del personal administratiu i el Servei d’atenció a l’estudiant, va assumir el repte d’incloure una nova assignatura en el pla docent del Grau de Farmàcia, que es va denominar “Pràctiques en empreses”.
En paral·lel a la posta en marxa d’aquesta assignatura, es va iniciar una nova activitat per assegurar que els estudiants escollirien adequadament la companyia/departament/lloc de treball i donar-los les nocions bàsiques per poder afrontar amb les millors garanties d’èxit l’entrevista laboral. Sota el nom “Passaport a la professió”, s’han programat una sèrie de deu sessions per cada any acadèmic. Aquestes sessions inclouen temes d’una amplia varietat per proveir als estudiants amb les eines bàsiques per aprofitar al màxim el període de practiques i afrontar amb èxit el seu futur professional quan acabin els estudis de grau. A més, s’han celebrat tres workshops i dos taules rodones per apropar el mon de l’empresa a la universitat. S’ha de destacar que el projecte s’ha ampliat a nivell internacional, ja que una empresa farmacèutica amb seu en el Regne Unit cada any contracta a dos o tres estudiants de grau durant un any.
Les dades estadístiques obtingudes en el procés s’han analitzat per tenir una millor comprensió de l’activitat i poder millorar el programa.REIRE Revista d'Innovació i Recerca en educacióUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/96743spacc-by (c) Escolano Mirón et al., 2015info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es/">http://creativecommons.org/licenses/by/3.0/es/</a>
oai:recercat.cat:2072/2619102018-02-10T06:31:08Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/261910Adaptive plasticity in the hippocampus of young mice intermittently exposed to MDMA could be the origin of memory deficits.Abad, SoniaCamarasa García, JordiPubill Sánchez, DavidCamins Espuny, AntoniEscubedo Rafa, ElenaÈxtasi (Droga)AmfetaminesHipocamp (Cervell)Trastorns de la memòriaRatolins (Animals de laboratori)Ecstasy (Drug)AmphetaminesHippocampus (Brain)Memory disordersMice (Laboratory animals)(±)3,4-Methylenedioxymethamphetamine (MDMA) is a relatively selective dopaminergic neurotoxin in mice. This study was designed to evaluate whether MDMA exposure affects their recognition memory and hippocampal expression of plasticity markers. Mice were administered with increasing doses of MDMA once per week for 8 weeks (three times in 1 day, every 3 h) and killed 2 weeks (2w) or 3 months (3m) later. The treatment did not modify hippocampal tryptophan hydroxylase 2, a serotonergic indicator, but induced an initial reduction in dopaminergic markers in substantia nigra, which remained stable for at least 3 months. In parallel, MDMA produced a decrease in dopamine (DA) levels in the striatum at 2w, which were restored 3 months later, suggesting dopaminergic terminal regeneration (sprouting phenomenon). Moreover, recognition memory was assessed using the object recognition test. Young (2w) and mature (3m) adult mice exhibited impaired memory after 24-h but not after just 1-h retention interval. Two weeks after the treatment, animals showed constant levels of CREB but an increase in its phosphorylated form and in c-Fos expression. Brain-derived neurotrophic factor (BDNF) and especially Arc overexpression was sustained and long-lasting. We cannot rule out the absence of MDMA injury in the hippocampus being due to the generation of BDNF. The levels of NMDAR2B, PSD-95, and synaptophysin were unaffected. In conclusion, the young mice exposed to MDMA showed increased expression of early key markers of plasticity, which sometimes remained for 3 months, and suggests hippocampal maladaptive plasticity that could explain memory deficits evidenced here.Humana PressUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/98696eng(c) Humana Press., 2015info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/3065372018-03-15T06:34:12Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/306537Studies on the Interaction of Isocyanides with Imines: Reaction Scope and Mechanistic VariationsGhashghaei, OuldouzManna, Consiglia AnnamariaVicente García, EstherRevés, MarcLavilla Grífols, RodolfoIsonitrilsIminesCompostos heterocíclicsReaccions químiquesQuímica orgànicaIsocyanidesIminesHeterocyclic compoundsChemical reactionsOrganic chemistryThe interaction of imines with isocyanides has been studied. The main product results from a sequential process involving the attack of two units of isocyanide, under Lewis acid catalysis, upon the carbon-nitrogen double bond of the imine to form the 4-membered ring system. The scope of the reaction regarding the imine and isocyanide ranges has been determined, and also some mechanistic variations and structural features have been described.Beilstein InstituteUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/120563engcc-by (c) Ghashghaei, Ouldouz et al., 2014info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3065382018-03-15T06:34:12Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/306538Multicomponent reaction access to complex quinolines via oxidation of the povarov adductsVicente García, EstherRamón, RosarioPreciado Gallego, SaraLavilla Grífols, RodolfoQuinoleïnaOxidacióSíntesi orgànicaQuinolineOxidationOrganic synthesisThe tetrahydroquinolines obtained through the Povarov multicomponent reaction have been oxidized to the corresponding quinoline, giving access to a single product through a two-step sequence. Several oxidizing agents were studied and manganese dioxide proved to be the reagent of choice, affording higher yields, cleaner reactions and practical protocols.Beilstein InstituteUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/120564engcc-by (c) Vicente García, Esther et al., 2011info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3065392018-03-15T06:34:13Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/306539Synthetic approaches to multifunctional indenesMesquida Estévez, Ma. NeusLópez Pérez, SaraDinarès Milà, M. ImmaculadaAlcalde Pais, Ma. Ermitas (María de las Ermitas)Síntesi orgànicaCompostos organometàl·licsCompostos policíclicsAmidesOrganic synthesisOrganometallic compoundsPolycyclic compoundsAmidesThe synthesis of multifunctional indenes with at least two different functional groups has not yet been extensively explored. Among the plausible synthetic routes to 3,5-disubstituted indenes bearing two different functional groups, such as the [3-(aminoethyl)inden-5-yl)]amines, a reasonable pathway involves the (5-nitro-3-indenyl)acetamides as key intermediates. Although several multistep synthetic approaches can be applied to obtain these advanced intermediates, we describe herein their preparation by an aldol-type reaction between 5-nitroindan-1-ones and the lithium salt of N,N-disubstituted acetamides, followed immediately by dehydration with acid. This classical condensation process, which is neither simple nor trivial despite its apparent directness, permits an efficient entry to a variety of indene-based molecular modules, which could be adapted to a range of functionalized indanones.Beilstein InstituteUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/120566engcc-by (c) Mesquida Estévez, Ma. Neus et al., 2011info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3068282018-03-17T06:29:33Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/306828El consumo excesivo de fructosa en el embarazo puede dañar la placenta y prococar estrés oxidativo en los fetosRodrigo, SilviaRodríguez, LourdesOtero, PaolaPanadero, María I.García, AntoniaBarbas, CoralRoglans i Ribas, NúriaRamos, SoniaGoya, LuisLaguna Egea, Juan CarlosÁlvarez-Millán, Juan J.Bocos, CarlosFructosaEmbaràsFructosePregnancyLa fructosa se utiliza para fabricar el sirope de maíz rico en fructosa (HFCS, en sus siglas en inglés), el cual se usa para edulcorar gran variedad de alimentos (comidas procesadas, bollería y repostería industrial, helados, mermeladas, salsas y condimentos) y, sobre todo, bebidas o refrescos azucarados. El consumo excesivo de estos alimentos, y por tanto de fructosa, se ha relacionado con la aparición de enfermedades como la obesidad, la diabetes y las enfermedades cardiovasculares [Tappy, 2010].Medigene PressUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/120829spacc-by (c) Rodrigo, Silvia et al., 2017info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3068292018-04-20T05:30:18Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/306829Breakthroughs in Medicinal Chemistry: New targets and mechanisms, new drugs, new hopesMuñoz-Torrero López-Ibarra, DiegoMangoni, Arduino A.Guillou, CatherineCollina, SimonaVanden Eynde, Jean JacquesRautio, JarkkoKeseru, György M.Hulme, ChristopherChibale, KellyLuque Garriga, F. XavierKaraman, RafikGütschow, MichaelLiu, HongRagno, RinoQuímica farmacèuticaPharmaceutical chemistryThe Editorial Board of the Medicinal Chemistry section of the journal Molecules publishes here its first Editorial, which has been prepared by highlighting, in sub-editorials of about one hundred words, some selected recently published articles that may have a profound impact on drug discovery and therapy. In particular, this editorial highlights new drug targets and mechanisms of action and new classes of drugs, as well as new therapeutic uses for known drugs or the involvement of known biological targets in new diseases. We also discuss some structural biology studies and new computational tools that may pave the way for the rational design or identification of more efficacious and safer drugs. Overall, the findings reported in these highlighted papers raise our hopes for the management of difficult-to-treat diseases that are posing a growing health threat, with new or repurposed drugs that overcome the limitations of currently applied therapies.MDPIUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/120834engcc-by (c) Muñoz-Torrero López-Ibarra, Diego et al., 2017info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/2506562018-04-28T05:31:42Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/250656Chapter One – Larock Reaction in the synthesis of heterocyclic compoundsHerraiz Cobo, JesúsAlbericio Palomera, FernandoÁlvarez Domingo, MercedesQuímica orgànicaSíntesi orgànicaCompostos heterocíclicsOrganic chemistryOrganic synthesisHeterocyclic compoundsThe indole ring is one of the most common features in natural products and small molecules with important bioactivity. Larock reported a new methodology for the synthesis of the indole ring system based on the palladium-catalyzed heteroannulation of 2-iodoaniline and substituted alkyne moieties. This procedure was subsequently extended to the preparation of other nitrogen- and oxygen- containing heterocycles. This is the process of choice for the synthesis of a large number of heterocyclic derivatives, as it provides outstanding regioselectivity and good to excellent yields.ElsevierUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/65732eng(c) Elsevier, 2015info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/3031232018-05-01T05:32:35Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/303123Neuroprotective Effects of β-Caryophyllene against Dopaminergic Neuron Injury in a Murine Model of Parkinson's Disease Induced by MPTPViveros-Paredes, Juan M.González-Castañeda, Rocio E.Gertsch, JuergChaparro-Huerta, VeronicaLópez-Roa, Rocio I.Vázquez-Valls, EduardoBeas Zárate, CarlosCamins Espuny, AntoniFlores-Soto, Mario E.Malaltia de ParkinsonNeurotoxinesParkinson's diseaseNeurotoxinsParkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by the loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that its pathogenesis is associated with oxidative stress and inflammation. Recent studies have suggested a protective role of the cannabinoid signalling system in PD. β-caryophyllene (BCP) is a natural bicyclic sesquiterpene that is an agonist of the cannabinoid type 2 receptor (CB2R). Previous studies have suggested that BCP exerts prophylactic and/or curative effects against inflammatory bowel disease through its antioxidative and/or anti-inflammatory action. The present study describes the neuroprotective effects of BCP in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced murine model of PD, and we report the results of our investigation of its neuroprotective mechanism in neurons and glial cells. In the murine model, BCP pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in the SN and striatum, and alleviated MPTP-induced glia activation. Additionally, BCP inhibited the levels of inflammatory cytokines in the nigrostriatal system. The observed neuroprotection and inhibited glia activation were reversed upon treatment with the CB2R selective antagonist AM630, confirming the involvement of the CB2R. These results indicate that BCP acts via multiple neuroprotective mechanisms in our murine model and suggest that BCP may be viewed as a potential treatment and/or preventative agent for PD.MDPIUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/118860engcc-by (c) Viveros-Paredes, Juan M. et al., 2017info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/1720802020-02-14T14:42:49Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/172080Piperidones: from alkaloids to PseudopeptidesForns i Berenguel, PilarRubiralta, Màrius (Rubiralta i Alcañiz)Diez Pascual, AnnaAlcaloidesSíntesi orgànicaAlkaloidsSynthetic organic chemistry[cat] Els nostres treballs inicials sobre la síntesi d'alcaloides que contenen un anell de piperidina en llur estructura, ens va portar a la preparació de sintons piperidínics diversament funcionalitzats sobre els quals construir molècules més complexes. Des de llavors hem sintetitzat algunes piperidones, que hem emprat per a la obtenció de compostos amb interès biològic. Al llarg dels anys, aquests compostos van des dels alcaloides fins a pseudopèptids de conformació restringida. Aquest article consta, per tant, d'una breu introducció històrica, seguida de vuit capítols corresponents als sintons piperidínics més rellevants que hem desenvolupat: i) 2-aril-4-piperidones, ii) ∆3-piperidein-2-ones i 2-ciano- ∆3-piperideïnes, iii) 3-amino-2-arilpiperidin-4- nes, iv) 3- aminopiperidin-2-ones, v) glutarimides, vi) enamides, vii) oxazolopiperidones i viii) hidroxilactams.[eng] Our earlywork on the synthesis of alkaloids that contain a piperidine ring led us to prepare diversely functionalised piperidines as scaffolds for building more complex structures. Since then we have prepared a number of piperidone synthons, and we have applied these to the preparation of biologically interesting compounds which range from alkaloids to conformationally constrained pseudopeptides. We provide here a brief historical introduction, followed by eight sections, dedicated to our most relevant piperidine synthons: i) 2-aryl-4-piperidones, ii) ∆3-piperidein-2-ones and 2-cyanopiperideines, iii) 3-amino-2-arylpiperidin-4-ones, iv) 3-aminopiperidin-2-ones, v) glutarimides, vi) 3-amino-∆5- piperidein-2-ones, vii) oxazolopiperidones, and viii) hydroxylactams.Institut d'Estudis CatalansUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/20535engcc-by (c) Forns et a., 2001info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3712442020-02-14T14:42:49Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/3712441,2,3,4-Tetrahydrobenzo[h][1,6]naphthyridines as a new family of potent peripheral-to-midgorge-site inhibitors of acetylcholinesterase: synthesis, pharmacological evaluation and mechanistic studiesDi Pietro, OrnellaViayna, ElisabetVicente García, EstherBartolini, ManuelaRamón, RosarioJuárez-Jiménez, JordiClos Guillén, M. VictòriaPérez Fernández, BelénAndrisano, VincenzaLuque Garriga, F. XavierLavilla Grífols, RodolfoMuñoz-Torrero López-Ibarra, DiegoAcetilcolinesterasaDisseny de medicamentsInhibidors enzimàticsMalaltia d'AlzheimerCompostos heterocíclicsAcetylcholinesteraseDrug designEnzyme inhibitorsAlzheimer's diseaseHeterocyclic compoundsA series of 1,2,3,4-tetrahydrobenzo[h][1,6]naphthyridines differently substituted at positions 1, 5, and 9 have been designed from the pyrano[3,2-c]quinoline derivative 1, a weak inhibitor of acetylcholinesterase (AChE) with predicted ability to bind to the AChE peripheral anionic site (PAS), at the entrance of the catalytic gorge. Fourteen novel benzonaphthyridines have been synthesized through synthetic sequences involving as the key step a multicomponent Povarov reaction between an aldehyde, an aniline and an enamine or an enamide as the activated alkene. The novel compounds have been tested against Electrophorus electricus AChE (EeAChE), human recombinant AChE (hAChE), and human serum butyrylcholinesterase (hBChE), and their brain penetration has been assessed using the PAMPA-BBB assay. Also, the mechanism of AChE inhibition of the most potent compounds has been thoroughly studied by kinetic studies, a propidium displacement assay, and molecular modelling. We have found that a seemingly small structural change such as a double O → NH bioisosteric replacement from the hit 1 to 16a results in a dramatic increase of EeAChE and hAChE inhibitory activities (>217- and >154-fold, respectively), and in a notable increase in hBChE inhibitory activity (> 11-fold), as well. An optimized binding at the PAS besides additional interactions with AChE midgorge residues seem to account for the high hAChE inhibitory potency of 16a (IC50 = 65 nM), which emerges as an interesting anti-Alzheimer lead compound with potent dual AChE and BChE inhibitory activities.Elsevier Masson SASUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/54915eng(c) Elsevier Masson SAS, 2014info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/3576762020-02-14T14:42:50Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/357676Origin of the Base-Dependent Facial Selectivity in Annulation Reactions of Nazarov-Type Reagents with Unsaturated Indolo[2,3-a] quinolizidine LactamsEstarellas, CarolinaArioli, FedericaPérez Bosch, MariaAre, CelesteHevia, DavidMolins i Grau, EliesLuque Garriga, F. XavierBosch Cartes, JoanAmat Tusón, MercedesTeoria del funcional de densitatIndicadors (Química)Proves i reactius químicsQuímica orgànicaDensity functionalsIndicators and test-papersChemical tests and reagentsOrganic chemistryMethyl-substituted Nazarov reagent 4 reacts stereoselectively with N-ind-Boc indoloquinolizidine lactams to give the expected 3-H/15-H cis pentacyclic yohimbine-type adducts when using 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU) as the base. However, a dramatic change of the facial selectivity was observed when the reaction was performed in the presence of Cs2CO3, leading to the corresponding trans adducts. This annulation is the key step of a stereocontrolled synthesis of the 17acarba analogue of the heteroyohimbine alkaloid akuammigine. Theoretical calculations were used to rationalize the facial selectivity of these double Michael addition reactions.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/135638eng(c) Wiley-VCH, 2017info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/3593732020-02-14T14:42:50Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/359373Current applications of nanoemulsions in cancer therapeutics.Sánchez-López, E. (Elena)Guerra, MarianaDias-Ferreira, JoãoLópez-Machado, AnaEttcheto, MirenCano, AmandaEspina García, MartaCamins Espuny, AntoniGarcía, Maria LuisaSouto, Eliana B.NanopartículesCàncerSistemes d'alliberament de medicamentsFarmacologia experimentalNanoparticlesCancerDrug delivery systemsExperimental pharmacologyNanoemulsions are pharmaceutical formulations composed of particles within a nanometer range. They possess the capacity to encapsulate drugs that are poorly water soluble due to their hydrophobic core nature. Additionally, they are also composed of safe gradient excipients, which makes them a stable and safe option to deliver drugs. Cancer therapy has been an issue for several decades. Drugs developed to treat this disease are not always successful or end up failing, mainly due to low solubility, multidrug resistance (MDR), and unspecific toxicity. Nanoemulsions might be the solution to achieve e cient and safe tumor treatment. These formulations not only solve water-solubility problems but also provide specific targeting to cancer cells and might even be designed to overcome MDR. Nanoemulsions can be modified using ligands of di erent natures to target components present in tumor cells surface or to escape MDR mechanisms. Multifunctional nanoemulsions are being studied by a wide variety of researchers in di erent research areas mainly for the treatment of di erent types of cancer. All of these studies demonstrate that nanoemulsions are e ciently taken by the tumoral cells, reduce tumor growth, eliminate toxicity to healthy cells, and decrease migration of cancer cells to other organs.MDPIUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/137101engcc-by (c) Sánchez-López, E. (Elena) et al., 2019info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3593742020-02-14T14:42:51Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/359374Enantioselective formal synthesis of (+)-madangamine AAre, CelestePérez Bosch, MariaBosch Cartes, JoanAmat Tusón, MercedesAlcaloidesLactamesCompostos heterocíclicsSíntesi orgànicaAlkaloidsLactamsHeterocyclic compoundsOrganic synthesisAn enantioselective formal synthesis of the marine alkaloid madangamine A using phenylglycinol-derived lactam 1 as the starting enantiomeric scaffold is reported. The synthesis involves the construction of the C-9 substituted diazatricyclic ABC core and the final closure of D and E rings from the polyunsaturated skipped intermediate 19.Royal Society of ChemistryUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/137117eng(c) Are, Celeste et al., 2019info:eu-repo/semantics/embargoedAccess
oai:recercat.cat:2072/3597462020-02-14T14:42:51Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/359746Memantine loaded PEGylated biodegradable nanoparticles for the treatment of glaucomaSánchez-López, E. (Elena)Egea Gras, Ma. AntoniaDavis, Benjamin MichaelGuo, LiEspina García, MartaSilva, AméliaCalpena Campmany, Ana CristinaSouto, Eliana B.Ravindran, NiveditaEttcheto, MirenCamins Espuny, AntoniGarcía López, María LuisaCordeiro, M. FrancescaGlaucomaNanopartículesSistemes d'administració de medicamentsGlaucomaNanoparticlesDrug delivery devicesGlaucoma is a multifactorial neurodegenerative disease associated with retinal ganglion cells (RGC) loss. Increasing reports of similarities in glaucoma and other neurodegenerative conditions have led to speculation that therapies for brain neurodegenerative disorders may also have potential as glaucoma therapies. Memantine is an N-methyl-d-aspartate (NMDA) antagonist approved for Alzheimer's disease treatment. Glutamate-induced excitotoxicity is implicated in glaucoma and NMDA receptor antagonism is advocated as a potential strategy for RGC preservation. This study describes the development of a topical formulation of memantine-loaded PLGA-PEG nanoparticles (MEM-NP) and investigates the efficacy of this formulation using a well-established glaucoma model. MEM-NPs <200 nm in diameter and incorporating 4 mg mL−1 of memantine were prepared with 0.35 mg mL−1 localized to the aqueous interior. In vitro assessment indicated sustained release from MEM-NPs and ex vivo ocular permeation studies demonstrated enhanced delivery. MEM-NPs were additionally found to be well tolerated in vitro (human retinoblastoma cells) and in vivo (Draize test). Finally, when applied topically in a rodent model of ocular hypertension for three weeks, MEM-NP eye drops were found to significantly (p < 0.0001) reduce RGC loss. These results suggest that topical MEM-NP is safe, well tolerated, and, most promisingly, neuroprotective in an experimental glaucoma model.Wiley-VCHUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/138262eng(c) Wiley-VCH, 2018info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/3602322020-02-14T14:42:52Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/360232Ethnopharmacological and chemical characterization of Salvia species used in Valencian traditional herbal preparationsMartínez Francés, VanessaHahn, EmelineRíos, SegundoRivera, DiegoReich, EikeVila Casanovas, RoserCañigueral i Folcarà, SalvadorSalviaPlantes medicinalsInvestigació farmacèuticaPaís ValenciàSalviaMedicinal plantsPharmaceutical researchValencian CommunityIn Valencia Region (Spain), some wild and cultivated sages are used for medicinal purposes. Among them, Salvia officinalis subsp. lavandulifolia (SL) is widely employed and known for production of Spanish sage oil and herbal products. Nevertheless, it shares the market with S. blancoana subsp. mariolensis (SB) and, to a lesser extent, with their hybrid S. x hegelmaieri (SH). The knowledge on these two species is far low and confusion between them is possible. The aim of the present paper is to improve the ethnopharmacological, morphological and chemical knowledge of these sages, and to contribute to setting up quality specifications for improving identification and distinction from other Salvia species, such as, S. officinalis subsp. officinalis, S. x auriculata and S. microphylla var. microphylla. Samples were collected in Valencia Region and surrounding mountain areas during the ethnopharmacological field work. Twenty-nine medicinal uses were reported for SL, 13 of them being also recorded for SB. Of particular interest is a homemade liquor, used as digestive and known as 'salvieta,' which is mainly prepared with SB. The macro- and microscopic characters are insufficient for identification of cut, crushed or powdered material. The study of the essential oil and a HPTLC (High Performance Thin Layer Chromatography) fingerprint of their extracts could help to distinguish SB from the other sages. The essential oil from dried aerial parts of SB (content: 1.8-4.5%) was characterized by GC-FID (Gas Chromatography with Flame Ionization Detector) and GC-MS (Gas Chromatography coupled to Mass Spectrometry) showing a composition close to that currently accepted for Spanish sage essential oil in the European Pharmacopoeia, ISO (International Standard Organization) and UNE (Una Norma Española) standards, with 1,8-cineole (13.7-45.7%) and camphor (12.1-28.6%) as major constituents. HPTLC methods, based on the analysis of hydroalcoholic and dichloromethane extracts, allowed to distinguish SB from other Salvia taxa currently found in Valencia region, except from its hybrid SH. This interdisciplinary study, that combines popular knowledge with botany and chemistry, allows to identify the raw herbal material from SB and to distinguish it from other Salvia species, ensuring a proper commercialization as herbal teas or for the preparation of spirits.Frontiers MediaUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/138566engcc-by (c) Martínez Francés, Vanessa et al., 2017info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3615922020-02-14T14:42:52Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/361592Environmental Enrichment Improves Cognitive Deficits, AD Hallmarks and Epigenetic Alterations Presented in 5xFAD Mouse Model.Griñán Ferré, ChristianIzquierdo, VanesaOtero Saura, EduardPuigoriol Illamola, DolorsCorpas Expósito, RubénSanfeliu i Pujol, CoralOrtuño Sahagún, DanielPallàs i Llibería, Mercè, 1964-Malalties neurodegenerativesEpigènesiMalaltia d'AlzheimerCognicióNeurodegenerative DiseasesEpigenesisAlzheimer's diseaseCognitionCumulative evidence shows that modifications in lifestyle factors constitute an effective strategy to modulate molecular events related to neurodegenerative diseases, confirming the relevant role of epigenetics. Accordingly, Environmental Enrichment (EE) represents an approach to ameliorate cognitive decline and neuroprotection in Alzheimer's disease (AD). AD is characterized by specific neuropathological hallmarks, such as β-amyloid plaques and Neurofibrillary Tangles, which severely affect the areas of the brain responsible for learning and memory. We evaluated EE neuroprotective influence on 5xFAD mice. We found a better cognitive performance on EE vs. Control (Ct) 5xFAD mice, until being similar to Wild-Type (Wt) mice group. Neurodegenerative markers as β-CTF and tau hyperphosphorylation, reduced protein levels whiles APPα, postsynaptic density 95 (PSD95) and synaptophysin (SYN) protein levels increased protein levels in the hippocampus of 5xFAD-EE mice group. Furthermore, a reduction in gene expression of Il-6, Gfap, Hmox1 and Aox1 was determined. However, no changes were found in the gene expression of neurotrophins, such as Brain-derived neurotrophic factor (Bdnf), Nerve growth factor (Ngf), Tumor growth factor (Tgf) and Nerve growth factor inducible (Vgf) in mice with EE. Specifically, we found a reduced DNA-methylation level (5-mC) and an increased hydroxymethylation level (5-hmC), as well as an increased histone H3 and H4 acetylation level. Likewise, we found changes in the hippocampal gene expression of some chromatin-modifying enzyme, such as Dnmt3a/b, Hdac1, and Tet2. Extensive molecular analysis revealed a correlation between neuronal function and changes in epigenetic marks after EE that explain the cognitive improvement in 5xFAD. Keywords: behavior, cognition, environmental enrichment, epigenetics, APP, Tau, oxidative stress, inflammationFrontiers MediaUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/140143engcc-by (c) Griñán Ferré, Christian et al., 2018info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3615932020-02-14T14:42:52Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/361593Heme Oxygenase-1 and Brain Oxysterols Metabolism Are Linked to Egr-1 Expression in Aged Mice Cortex, but Not in HippocampusRosa, PaoloZerbinati, ChiaraCrestini, AlessioCanudas Teixidó, Anna-MariaRagona, GiuseppeConfaloni, AnnamariaIuliano, LuigiCalogero, AntonellaEnvellimentMalalties neurodegenerativesEnvelliment cerebralAgingNeurodegenerative DiseasesAging brainThroughout life, stress stimuli act upon the brain leading to morphological and functional changes in advanced age, when it is likely to develop neurodegenerative disorders. There is an increasing need to unveil the molecular mechanisms underlying aging, in a world where populations are getting older. Egr-1 (early growth response 1), a transcriptional factor involved in cell survival, proliferation and differentiation - with a role also in memory, cognition and synaptic plasticity, can be implicated in the molecular mechanism of the aging process. Moreover, Heme Oxygenase-1a (HO), a 32 kDa heat-shock protein that converts heme to iron, carbon monoxide and biliverdin, is a key enzyme with neuroprotective properties. Several in vitro and in vivo studies reported that HO-1 could regulate the metabolism of oxysterols, oxidation products of cholesterol that include markers of oxidative stress. Recently, a link between Egr-1 and HO-1 has been demonstrated in mouse lung cells exposed to cigarette smoke. In view of these data, we wanted to investigate whether Egr-1 can be implicated also in the oxysterol metabolism during brain aging. Our results show that Egr-1 expression is differently expressed in the cortex and hippocampus of old mice, as well as the oxysterol profile between these two brain areas. In particular, we show that the cortex experiences in an age-dependent fashion increasing levels of the Egr-1 protein, and that these correlate with the level of HO-1 expression and oxysterol abundance. Such a situation was not observed in the hippocampus. These results are further strenghtened by our observations made with Egr-1 KO mice, confirming our hypothesis concerning the influence of Egr-1 on oxysterol production and accumulation via regulation of the expression of HO-1 in the cortex, but not the hippocampus, of old mice. It is important to notice that most of the oxysterols involved in this process are those usually stimulated by oxidative stress, which would then represent the triggering factor for this mechanism. Keywords: Egr-1, aging brain, oxysterols, HO-1, oxidative stress, cortex, hippocampusFrontiers MediaUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/140151engcc-by (c) Rosa, Paolo et al., 2018info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3615942020-02-14T14:42:53Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/361594Temporal Integrative Analysis of mRNA and microRNAs Expression Profiles and Epigenetic Alterations in Female SAMP8, a Model of Age-Related Cognitive DeclineCosín Tomàs, MartaAlvarez-López, Maria J.Companys Alemany, JúliaKaliman, PerlaGonzález Castillo, CeliaOrtuño Sahagún, DanielPallàs i Llibería, Mercè, 1964-Griñán Ferré, ChristianEpigènesiEnvellimentEnvelliment cerebralMalaltia d'AlzheimerEpigenesisAgingAging brainAlzheimer's diseaseA growing body of research shows that epigenetic mechanisms are critically involved in normal and pathological aging. The Senescence-Accelerated Mouse Prone 8 (SAMP8) can be considered a useful tool to better understand the dynamics of the global epigenetic landscape during the aging process since its phenotype is not fully explained by genetic factors. Here we investigated dysfunctional age-related transcriptional profiles and epigenetic programming enzymes in the hippocampus of 2- and 9-month-old SAMP8 female mice using the Senescent-Accelerated Resistant 1 (SAMR1) mouse strain as control. SAMP8 mice presented 1,062 genes dysregulated at 2 months of age, and 1,033 genes at 9 months, with 92 genes concurrently dysregulated at both ages compared to age-matched SAMR1. SAMP8 mice showed a significant decrease in global DNA methylation (5-mC) at 2 months while hydroxymethylation (5-hmC) levels were increased in SAMP8 mice at 2 and 9 months of age compared to SAMR1. These changes were accompanied by changes in the expression of several enzymes that regulate 5-mC and methylcytosine oxidation. Acetylated H3 and H4 histone levels were significantly diminished in SAMP8 mice at 2-month-old compared to SAMR1 and altered Histone DeACetylase (HDACs) profiles were detected in both young and old SAMP8 mice. We analyzed 84 different mouse miRNAs known to be altered in neurological diseases or involved in neuronal development. Compared with SAMR1, SAMP8 mice showed 28 and 17 miRNAs differentially expressed at 2 and 9 months of age, respectively; 6 of these miRNAs overlapped at both ages. We used several bioinformatic approaches to integrate our data in mRNA:miRNA regulatory networks and functional predictions for young and aged animals. In sum, our study reveals interplay between epigenetic mechanisms and gene networks that seems to be relevant for the progression toward a pathological aging and provides several potential markers and therapeutic candidates for Alzheimer's Disease (AD) and age-related cognitive impairment.Frontiers MediaUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/2445/140217engcc-by (c) Cosín Tomàs, Marta et al., 2018info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by/3.0/es">http://creativecommons.org/licenses/by/3.0/es</a>
oai:recercat.cat:2072/3615952020-02-14T14:42:53Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/361595Electrochemical preparation and characterization of magnetic core-shell nanowires for biomedical applicationsGispert, C.Serrà i Ramos, AlbertAlea Reyes, María ElisaRodrigues, Ana Mafalda NunesGómez, ElviraMora Giménez, MargaritaSagristá Gratovil, M. LluïsaPérez García, M. Lluïsa (Maria Lluïsa)Vallés Giménez, ElisaElectroquímicaNanoestructuresElectrochemistryNanostructuresMagnetic CoNi@Au coreshell nanorods have been electrochemically synthesized, characterized and functionalized to test their inherent cytotoxicity in order to assess their potential use for biomedical applications. The initially electrodeposited CoNi nanorods have been covered with a gold layer bymeans of galvanic displacement to minimize the nanowires toxicity and their aggregation, and favour the functionalization. The presence of a gold layer on the nanorod surface slightlymodifies themagnetic behaviour of the asdeposited nanorods, maintaining their softmagnetic behaviour and high magnetization of saturation. The complete covering of the nanorodswith the gold shell favours a good functionalization with a layer of (11Mercaptoundecyl) hexa(ethylene glycol)molecules, in order to create a hydrophilic coating to avoid the aggregation of nanorods, keeping themin suspension and give them stability in biological media. The presence of the organic layer incorporated was detected by means of electrochemical probe experiments. A cytotoxicity test of functionalized coreshell nanorods, carried out with adherent HeLa cells, showed that cell viability was higher than 80% for amounts of nanorods up to 10 μgmL−1. These results make functionalized nanorods promising vehicles for targeted drug delivery inmedicine, which gives a complementary property to the magnetic nanoparticles. © 2015 Elsevier B.V. All rights reserved.Elsevier B.V.Universitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/140430engcc-by-nc-nd (c) Elsevier B.V., 2015info:eu-repo/semantics/openAccess<a href="http://creativecommons.org/licenses/by-nc-nd/3.0/es">http://creativecommons.org/licenses/by-nc-nd/3.0/es</a>
oai:recercat.cat:2072/3619422020-02-14T14:42:53Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/361942Behavioral and Cognitive Improvement Induced by Novel Imidazoline I2 Receptor Ligands in Female SAMP8 MiceGriñán Ferré, ChristianVasilopoulou, FoteiniAbás Prades, SòniaRodríguez-Arévalo, SergioBagan Polonio, AndreaSureda, Francesc X.Pérez, BelénCallado, Luis F.García-Sevilla, Jesús A.García-Fuster, M. JuliaEscolano Mirón, CarmenPallàs i Llibería, Mercè, 1964-Malaltia d'AlzheimerMalalties neurodegenerativesEnvellimentAlzheimer's diseaseNeurodegenerative DiseasesAgingAs populations increase their life expectancy, age-related neurodegenerative disorders such as Alzheimer's disease have become more common. I2-Imidazoline receptors (I2-IR) are widely distributed in the central nervous system, and dysregulation of I2-IR in patients with neurodegenerative diseases has been reported, suggesting their implication in cognitive impairment. This evidence indicates that high-affinity selective I2-IR ligands potentially contribute to the delay of neurodegeneration. In vivo studies in the female senescence accelerated mouse-prone 8 mice have shown that treatment with I2-IR ligands, MCR5 and MCR9, produce beneficial effects in behavior and cognition. Changes in molecular pathways implicated in oxidative stress, inflammation, synaptic plasticity, and apoptotic cell death were also studied. Furthermore, treatments with these I2-IR ligands diminished the amyloid precursor protein processing pathway and increased Aβ degrading enzymes in the hippocampus of SAMP8 mice. These results collectively demonstrate the neuroprotective role of these new I2-IR ligands in a mouse model of brain aging through specific pathways and suggest their potential as therapeutic agents in brain disorders and age-related neurodegenerative diseases. Keywords Imidazoline I2 receptors (2-imidazolin-4-yl)phosphonates Behavior Cognition Neurodegeneration Neuroprotection AgingSpringer VerlagUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/140738eng(c) American Society for Experimental NeuroTherapeutics, 2018info:eu-repo/semantics/openAccess
oai:recercat.cat:2072/3712452020-02-14T14:42:54Zhdl_2072_1718112024-03-28T18:09:16Z urn:hdl:2072/371245Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agentsViayna, ElisabetSola, IreneBartolini, ManuelaDe Simone, AngelaTapia-Rojas, CherilSerrano, Felipe G.Sabaté Lagunas, RaimonJuárez-Jiménez, JordiPérez Fernández, BelénLuque Garriga, F. XavierAndrisano, VincenzaClos Guillén, M. VictòriaInestrosa, Nibaldo C.Muñoz-Torrero López-Ibarra, DiegoCompostos orgànicsDisseny de medicamentsInhibidors enzimàticsMalaltia d'AlzheimerQuimioteràpiaOrganic compoundsDrug designEnzyme inhibitorsAlzheimer's diseaseChemotherapyWe have synthesized a family of rhein-huprine hybrids to hit several key targets for Alzheimer"s disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase butyrylcholinesterase, and BACE-1, dual Aβ42 and tau anti-aggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and (-)-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction , preventing the loss of synaptic proteins and/or have a positive effect on the induction of long term potentiation. In vivo studies in APP-PS1 transgenic mice treated i.p. for 4 weeks with (+)- and (-)-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and (-)-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.American Chemical SocietyUniversitat de Barcelonainfo:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/2445/54947eng(c) American Chemical Society , 2014info:eu-repo/semantics/openAccess
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