3D-QSAR analysis of a series of S-DABO derivatives as anti-HIV agents by CoMFA and CoMSIA.

In this study, we retrieved a series of 59 dihydroalkylthio-benzyloxopyrimidine (S-DABO) derivatives, which is a class of highly potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) reported from published articles, and analysed them with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Statistically significant three-dimensional quantitative structure-activity relationship (3D-QSAR) models by CoMFA and CoMSIA were derived from a training set of 46 compounds on the basis of the rigid body alignment. Further, the predictive ability of the QSAR models was validated by a test set of 13 compounds. Based on the information derived from CoMFA and CoMSIA contour maps, we have identified some steric and electrostatic features for improving the activities of these inhibitors, and we validated the 3D-QSAR results by a molecular docking method. On the basis of the obtained results, we designed a new series of S-DABO derivatives with high activities. Therefore, this study could be utilized to design more potent S-DABO analogues as anti-HIV agents.