THREE-DIMENSIONAL QUANTITATIVE STRUCTURE ACTIVITY RELATIONSHIP STUDIES ON DIVERSE STRUCTURAL CLASSES OF NATURAL FLAVONOIDS AS AMV AND HIV REVERSE TRANSCRIPTASE INHIBITORS USING CoMFA AND CoMSIA

摘要

In this study, comparative molecular ?eld analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed on a series of 73 experimentally reported natural flavonoid derivatives as AMV and HIV Reverse transcriptase (RT) inhibitors with pIC₅₀ values ranging from 4.00 to 5.92. Based on alignment, highly predictive CoMFA and CoMSIA were obtained with cross-validated q2value of 0.760 and 0.696 respectively, and non-cross-validated partial least-squares (PLS) analysis with the optimum components of ?ve showed a conventional r2 of 0.964 and 0.977 respectively. The CoMFA and CoMSIA models have been further validated for their stability and robustness using group validation and boot-strapping techniques and for their predictive abilities. The analysis of CoMFA contour maps provided insight into the possible modi?cation of the molecules for better activity.