Derivados de cromenopirazoles como ligandos de receptores de cannabinoides

Derivados de cromenopirazoles como ligandos de receptores de cannabinoides. Compuestos derivados de cromenopirazoles que son ligandos de receptores de cannabinoides, su uso para la fabricación de un medicamento, uso de este medicamento para el tratamiento y/o la prevención de trastornos asociados a los receptores de cannabinoides, uso de dicho compuesto como reactivo en ensayos biológicos relacionados con receptores de cannabinoides y procedimiento de obtención de los mismos.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Universidad Complutense de MadridA1 Solicitud de patente con informe sobre el estado de la técnic

N-benzyl 4,4-disubstituted piperidines as a potent class of influenza H1N1 virus inhibitors showing a novel mechanism of hemagglutinin fusion peptide interaction

The influenza virus hemagglutinin (HA) is an attractive target for antiviral therapy due to its essential role in mediating virus entry into the host cell. We here report the identification of a class of N-benzyl- 4,4,-disubstituted piperidines as influenza A virus fusion inhibitors with specific activity against the H1N1 subtype. Using the highly efficient one-step Ugi four-component reaction, diverse library of piperidine-based analogues was synthesized and evaluated to explore the structure-activity relation- ships (SAR). Mechanistic studies, including resistance selection with the most active compound (2) demonstrated that it acts as an inhibitor of the low pH-induced HA-mediated membrane fusion process. Computational studies identified an as yet unrecognized fusion inhibitor binding site, which is located at the bottom of the HA2 stem in close proximity to the fusion peptide. A direct p-stacking interaction between the N-benzylpiperidine moiety of 2 and F9HA2 of the fusion peptide, reinforced with an addi- tional p-stacking interaction with Y119HA2, and a salt bridge of the protonated piperidine nitrogen with E120HA2, were identified as important interactions to mediate ligand binding. This site rationalized the observed SAR and provided a structural explanation for the H1N1-specific activity of our inhibitors. Furthermore, the HA1-S326V mutation resulting in resistance to 2 is close to the proposed new binding pocket. Our findings point to the N-benzyl-4,4,-disubstituted piperidines as an interesting class of influenza virus inhibitors, representing the first example of fusion peptide binders with great potential for anti-influenza drug development

Novel indolic AMPK modulators induce vasodilatation through activation of the AMPK-eNOS-NO pathway

Endothelial adenosine monophosphate-activated protein kinase (AMPK) plays a critical role in the regulation of vascular tone through stimulating nitric oxide (NO) release in endothelial cells. Since obesity leads to endothelial dysfunction and AMPK dysregulation, AMPK activation might be an important strategy to restore vascular function in cardiometabolic alterations. Here, we report the identification of a novel AMPK modulator, the indolic derivative IND6, which shows affinity for AMPKα1β1γ1, the primary AMPK isoform in human EA.Hy926 endothelial cells. IND6 shows inhibitory action of the enzymatic activity in vitro, but increases the levels of p-Thr174AMPK, p-Ser1177eNOS and p-Ser79ACC in EA.Hy926. This paradoxical finding might be explained by the ability of IND6 to act as a mixed-type inhibitor, but also to promote the enzyme activation by adopting two distinct binding modes at the ADaM site. Moreover, functional assays reveal that IND6 increased the eNOS-dependent production of NO and elicited a concentration-dependent vasodilation of endothelium-intact rat aorta due to AMPK and eNOS activation, demonstrating a functional activation of the AMPK-eNOS-NO endothelial pathway. This kinase inhibition profile, combined with the paradoxical AMPK activation in cells and arteries, suggests that these new chemical entities may constitute a valuable starting point for the development of new AMPK modulators with therapeutic potential for the treatment of vascular complications associated with obesity

Glicosil hidrolasas de Lactiplantibacillus plantarum WCFS1

Resumen del trabajo presentado a la 15ª Reunión de la Red Española de Bacterias Lácticas: Bacterias Lácticas en Alimentación y Salud. Valencia, 26 y 27 de mayo de 2022.AGL2017-84614-C2-1-R y AGL2017-84614-C2-2-RPeer reviewe

Curs 0: preparació per als estudis a l’EEBE

Aquest article presenta el desenvolupament i primers resultats d'ús d'un conjunt de cursos virtuals que pretenen proporcionar uns coneixements inicials bàsics de Matemàtiques, Física i !ímica als estudiants que accedeixen a estudis de grau a l'Escola d'Enginyeria de Barcelona Est (EEBE). Els cursos han estat desenvolupats sobre la plataforma Atenea (Moodle). El seu nucli el constitueixen un conjunt de materials per a autoaprenentatge que inclouen documents escrits, vídeos i tests d'autoavaluació. Els documents escrits i els vídeos corresponen tant a explicacions de teoria com a la resolució detallada d'exercicis. En el marc d'una prova pilot, els cursos, de seguiment voluntari durant el període transcorregut entre la matricula (mitjans de juliol) i l'inici de les classes (mitjans de setembre), van ser publicitats a tots els estudiants de nou accés del curs 2021-2022. Encara que la participació va ser més limitada del que s'esperava (únicament el 22% dels estudiants de nou accés es van inscriure), cal destacar que els estudiants que sí que van seguir els cursos van expressar majoritàriament una bona valoració dels mateixos (al respondre un qüestionari de satisfacció). Del desenvolupament dels cursos i de la realització de la prova pilot s'han obtingut unes quantes conclusions que també queden reflectides al final de l'article

Nuevos ligandos del receptor Sigma-1 y de los receptores cannabinoides CB1 y CB2 como potenciales compuestos analgésicos

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias y CSIC. Fecha de lectura: 19-07-201

Catálogo del Museo Armería de José Estruch

Copia digital. España : Ministerio de Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 202

Tautomerism of hydroxychromenopyrazoles

Annular tautomerism (OH⋯N and/or NH⋯O) of hydroxychromenopyrazoles was studied by NMR-spectroscopy and B3LYP/6-311++G(d,p) theoretical calculations. The experimental chemical shifts of 4,4-dimethyl-7-pentyl-2,4-dihydrochromeno[4,3-c]pyrazol-9-ol have been compared with absolute shieldings calculations performed using the GIAO approximation. This study shows that the title compound exists mainly as an OH⋯N tautomer in solution. © 2012 Elsevier B.V. All rights reserved.Peer Reviewe

Derivados de cromenopirazoles como ligandos de receptores de cannabinoides.

[EN] The invention relates to compounds derived from cromenopyrazoles that are cannabinoid receptor ligands, to the use thereof for the production of a drug, to the use of this drug in the treatment and/or prevention of disorders associated with cannabinoid receptors, to the use of said compound as a reagent in biological assays related to cannabinoid receptors, and to the method for obtaining same.[ES] Compuestos derivados de cromenopirazoles que son ligandos de receptores de cannabinoides, su uso para la fabricación de un medicamento, uso de este medicamento para el tratamiento y/o la prevención de trastornos asociados a los receptores de cannabinoides, uso de dicho compuesto como reactivo en ensayos biológicos relacionados con receptores de cannabinoides y procedimiento de obtención de los mismos.Peer reviewedConsejo Superior de Investigaciones Científicas (España), Universidad Complutense de MadridA1 Solicitud de patente con informe sobre el estado de la técnic

Preparation of 2,2-dimethylchroman-4-ones from 5-alkyl-substituted resorcinols: Microwave-assisted synthesis and theoretical calculations

The influence of different 5-alkyl-substituted resorcinols on the formation of 2,2-dimethylchroman- 4-ones is examined experimentally and theoretically. Structures are fully assigned by means of experimental and theoretical 13C and 1H NMR chemical shifts. Based on experimental and theoretical calculations of Friedel-Crafts acylation, it is possible to explain the formation of 2,2-dimethyl-5-hydroxychroman-4-ones and/or 2,2-dimethyl-7-hydroxychroman-4- ones. Evaluation of their biological activity as cannabinoid receptor ligands is also reported. © ARKAT-USA, Inc.Peer Reviewe