2D, 3D-QSAR and docking studies of 1,2,3-thiadiazole thioacetanilides analogues as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

ABSTRACT: BACKGROUND: The discovery of clinically relevant inhibitors of HIV-RT for antiviral therapy has proven to be a challenging task. To identify novel and potent HIV-RT inhibitors the quantitative structure-activity relationship (QSAR) approach became very useful and largely widespread technique for ligand based drug design. METHODS: We perform the two- and three-dimensional (2D and 3D) QSAR studies of a series of 1,2,3-Thiadiazole thioacetanilides Analogues to elucidate the structural properties required for HIV-RT inhibitory activity. RESULTS: The 2D-QSAR studies were performed using multiple linear regression method (MLR), giving r2 = 0.97 and q2 = 0.94. The 3D-QSAR studies were performed using the stepwise variable selection k-nearest neighbor molecular field analysis approach; a leave-one-out cross-validated correlation coefficient q2=0.89 and a non-cross-validated correlation coefficient r2=0.97 were obtained. Docking analysis suggests the new series have comparable binding affinity with the standard compounds. CONCLUSIONS: This approach showed that hydrophobic & electrostatic effects dominantly determine binding affinities which will further useful for development of new NNRTIs.