Estudio in Sílico: acoplamiento molecular del receptor GABA-A con distintos ligantes de núcleo Benzodiacepínico, para el diseño de un análogo de la familia de fármacos BZDS.

Abstract

Benzodiazepines are a family of drugs, with anxiolytic, sedative, anticonvulsant and hypnotic properties, which have been widely used in the clinical setting. Consequently, in the present work a theoretical computational study was carried out with different commercial benzodiazepines, which were later modified to increase their affinity with the γ-aminobutyric acid receptor. For this, the method known as virtual screening based on the structure was used, in which the Avogadro program was used in order to optimize the different structures that were designed, likewise the AutoDock Tools and AutoDock Vina software was used to perform the study of molecular coupling (Docking) between the selected benzodiazepines and the GABA-A receptor. Subsequently, with the 381 structural modifications that were carried out, 12 structures were taken that presented better results to carry out their respective toxicological analysis using PreADMET. Of these 12 structures, the best ones were selected and their respective retrosynthesis and subsequent synthesis were proposed for each one, and they were considered as possible analogues to the benzodiazepine family.