Inhibidores no simétricos de colina quinasa con actividad antitumoral y antimalárica

Número de publicación: ES2472367 B1. Número de solicitud: 201300033.La presente invención se enmarca en el campo farmacéutico, concretamente la invención se refiere a compuestos no simétricos de bispiridinio inhibidiores de la enzima colina quinasa, su síntesis y su uso como medicamento antitumoral y/o antiparasitario.Universidad de Granad

Unbinding Pathways from the Glucocorticoid Receptor Shed Light on the Reduced Sensitivity of Glucocorticoid Ligands to a Naturally Occurring, Clinically Relevant Mutant Receptor

Glucocorticoids are endogenous steroid hormones that regulate essential biological functions, including metabolism, growth, and apoptosis. Glucocorticoids represent the most effective anti-inflammatory agents for the treatment of several inflammatory conditions. However, the clinical use of such drugs is hampered by severe side effects. Therefore, the development of novel glucocorticoid receptor (GR) modulators with an increased therapeutic index is impelling. Herein, using steered molecular dynamics (SMD) simulations, we provide a detailed picture of the unbinding process of three clinically relevant GR modulators from GR ligand binding domains. The SMD protocol described here can be used to prioritize the synthesis of structural analogues on the basis of their potentials of mean force and calculated unbinding energies. Moreover, our results are instrumental in explaining at atomic resolution the weakened ability of dexamethasone to activate the naturally occurring mutant I747M GR, which is implicated in rare familial glucocorticoid resistance, clinically characterized by glucocorticoid insensitivity

1H, 13C NMR, X-ray and conformational studies of new 1-alkyl-3-benzoyl-pyrazole and 1-alkyl-3-benzoyl-pyrazoline derivatives

Spectral Assignments and Reference DataThe 1H and 13C NMR resonances of 22 1-alkyl-pyrazole and 25 1-alkyl-pyrazoline derivatives were assigned completely using the concerted application of one- and two-dimensional experiments (DEPT, gs-HMQC and gs-HMBC). Nuclear Overhauser enhancement (NOE) effects, conformational analysis and X-ray crystallography confirm the preferred conformation of those compounds.This work was partially supported by grants from theMinisterio de CienciayTecnología(SAF2005-07991-C02-01andSAF2005-07991- C02-02) and from the Junta de Andalucia (P06-CTS-01941). Duane Choquesillo-Lazarte thanks Consejo Superior Investigaciones Cientificas – European Union for an I3P postdoctoral research contractPeer reviewe

Inhibidores polares simétricos de colina cinassa con actividad antitumoral

Número de publicación: ES2482290 B1. Número de solicitud: 201400466.La invención se refiere a compuestos polares simétricas de bispyridinium, bisquinuclidinium y bisquinolinium con un enlazador derivado de 1,2-bis (p-toliloxi) etano, que son inhibidores de colina quinasa. La invención también se refiere a la síntesis de los mismos y al uso de los mismos como medicamentos antitumorales.Universidad de Granad

New more polar symmetrical bipyridinic compounds: new strategy for the inhibition of choline kinase \u3b11

Aim: Research of the antitumor properties of biscationic compounds has received significant attention over the last few years. Results: A novel family of 1,1′-([2,2′-bipyridine]-5,5′-diylbis(methylene))bis-substituted bromide (9a-k), containing two nitrogen atoms in the linker, considered as hypothetical hydrogen bond acceptors, were synthesized and evaluated as ChoK inhibitors and their antiproliferative activity against six cancer cell lines. Conclusion: The most promising compounds in this series are 1,1′-([2,2′-bipyridine]-5,5′-diylbis(methylene))bis(4-(methyl(phenyl)amino)-quinolinium bromide derivatives 9g-i (analogs to RSM932A), that significantly inhibit cancer cell growth at even submicromolar concentrations, especially against leukemia cells. Compounds 9g-i also inhibit the ChoKα1 with good or moderate values, as predicted by initial docking studies. In addition, the most active compound 9h remarkably induces apoptosis in two cell lines following the mitochondrial pathway. </jats:p

Utilización y aplicación de la herramienta "google docs" en la docencia universitaria dentro del marco del EEES

Como consecuencia de la realización del curso 'Aplicaciones de la Web 2.0 en la Investigación y la Docencia' organizado por La Fundación General Universidad de Granada-Empresa en el curso académico 2009-2010, los autores del presente trabajo presentamos el Proyecto de Innovación Docente concedido por el Vicerrectorado para la Garantía de la calidad de la Universidad de Granada,titulado 'Utilización de la herramienta “Google Docs” en la Docencia Universitaria dentro del marco del EEES. Creemos que el proyecto tiene un diseño aplicable a cualquier asignatura de la actual Licenciatura y/o Grado de Farmacia. En este trabajo se expone la experiencia piloto llevada a cabo en la asignatura de Química Farmacéutica, incluyendo el desarrollo, objetivos, metodología, resultados y las conclusiones que se están obteniendo en el trascurso del mism