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

ABSTRACT: UNLABELLED: 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 forligand-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, 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 that the new series have comparable binding affinity with the standard compounds. CONCLUSIONS:This approach showed that hydrophobic and electrostatic effects dominantly determine binding affinities which will further useful for development of new NNRTIs.

SUBMITTER: Jain SV 

PROVIDER: S-EPMC3495901 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature