Doença de alzheimer: estudos in silico de inibidores da proteina caspase 3

Abstract

Caspase 3 is an enzyme that plays an important role in programmed cell death (apoptosis). Its unbridled activation in neural cells, increasingly studied, is linked to one of the causes of neuron loss in Alzheimer's Disease (AD). Thus, this target is considered a promising target for the development of new drugs. That said, in this work a 2D quantitative structure-activity relationship (QSAR-2D) study was carried out based on 71 compounds described in the literature as caspase 3 inhibitors. The model obtained, using regression by PLS, was approved in terms of internal validation and external, and was used to predict new molecules from a virtual screening study based on 2D and later 3D similarity. After evaluating the toxicity and pharmacokinetic properties, 23 promising compounds were identified as potential caspase 3 inhibitors. These results provide important subsidies for future in vitro studies, aiming at the development of new treatments for AD. The computational approach used in this study demonstrated its effectiveness in identifying compounds with potential biological activity, contributing to optimize the discovery process of new drugs aimed at the treatment of AD.