2D QSAR Study of Some TIBO Derivatives as an Anti HIV Agent

Abstract

A set of sixteen Tetraimidazolebenzodiazepine -1- one (TIBO) derivatives with inhibitory concentration (pIC50) activity was subjected to the two dimensional quantitative structure activity relationships studies using computational drug design. Drug Designing module contain various combinations of physiochemical, electronic, topological and indicator parameter. TIBO taken as the lead molecule and QSAR model developed using multiple regression approach. For each set of descriptors, the best multilinear QSAR equations were obtained by the stepwise variable selection method using leave-one out cross-validation as selection criterion. Value of pIC50 was taken as dependent variable and physiochemical and topological parameter was taken as independent variable. The best QSAR model (r² = 0.9672, Fisher test value F=38.706, Se = 0.2628) has acceptable statistical quality and predictive potential. From the build model it seems to be clear that indicator parameter (presence of halogen atom at X position) and Balaban index along with Molecular Refractivity (MR) of the molecule is very much responsible in the binding affinity of anti HIV drug. Thus this validated model brings important structural insight to aid the design of novel anti HIV agents.