3D-QSAR studies of natural flavonoid compounds as reverse transcriptase inhibitors

Abstract

The three-dimensional quantitative structure–activity relationship (3D-QSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) were conducted on a series of 44 flavonoid compounds which exhibited in vitro avian myeloblastosis virus-reverse transcriptase (AMV-RT) inhibitory activity. The best predictive CoMFA model gives cross-validated r2 (q2) = 0.665, non-cross-validated r2 = 0.983, standard error of estimate (S) = 0.047, and F = 357.438. The best CoMSIA model has q2 = 0.685, non-cross-validated r2 = 0.963, S = 0.070, and F = 159.764, including steric, electrostatic, hydrogen bond donor, and acceptor fields. The predictive ability of these models was validated by a set of 11 compounds that were not included in the training set. The calculated (predicted) and experimental inhibitory activities were well correlated. Both CoMFA and CoMSIA models suggest fruitful structural insight to design more active compounds. In order to investigate the activity against HIV 1-RT comparing with AMV-RT, the docking simulation of some flavonoids with HIV 1-RT was performed. The flavonoids with good AMV-RT inhibitory activity also showed good binding energies with HIV 1-RT.