QSAR Study on Pyridinone Derivatives as HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor: A Mixed Approach

摘要

HIV-1 reverse transcriptase inhibitory activity of a series of substituted pyridinone derivatives (nonnucleoside) was subjected to classical QSAR study by using mixed approach (Hansch and Free-Wilson). The study was carried out with indicator parameter encoding different group contributions and some physico chemical parameters namely hydrophobic (π), electronic (), steric (MR) and STERIMOL values of aromatic substitutents. The best generated models were validated by leave-one- out technique (LOO-internal validation) and predicting the activity of the test (external validation). Further bootstrapping method was adopted to assess the robustness of the models. The analysis explores the substitutional requirements of the pyridinone moiety of the compounds for effective inhibition of HIV-1 RT enzyme.