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 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 r ² = 0.97 and q ² = 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 q ² = 0.89 and a non-cross-validated correlation coefficient r ² = 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.