2D QSAR STUDY OF FUSED 5,6-BICYCLIC HETEROCYCLES AS ANTI ALZHEIMER’S AGENTS USING TOPOLOGICAL PARAMETERS

Abstract

Alzheimer’s disease (AD) is a degrading and irreversible neurodegenerative disorder associated with loss of brain functions. It is manifested clinically into psychological symptoms that collectively form cognitive dysfunction and the loss of thinking skills through the progressive degeneration of central nervous system neurons. Over the last decade, γ-secretase emerged as a promising target for the treatment of Alzheimer’s disease. The γ-secretase modulator compounds would be good candidates for AD therapeutics. In previous years, a series fused 5,6-bicyclic heterocycles were investigated as γ-secretase modulators or anti Alzheimer’s agents. In the present study, a quantitative structure activity relationship (QSAR) study of twenty-eight derivatives of fused 5,6-bicyclic heterocycles has been made with the help of topological parameters. The descriptors that have been used are solvent accessible surface area, valence connectivity indices of order 0, 1 and 2 and shape indices of order 1, 2 and 3. The best QSAR model for this set of derivatives has been obtained by using solvent accessible surface area as first descriptor, valence connectivity index (order-0) as second descriptor, valence connectivity index (order-1) as third descriptor and shape index (order-3) as fourth descriptor. The correlation coefficient (r 2 ) and cross validation coefficient (rCV2 ) for this model are 0.773037 and 0.688568, respectively.