Thiocarbamates as non-nucleoside HIV-1 reverse transcriptase inhibitors: docking-based CoMFA and CoMSIA analyses.

Thiocarbamates (TCs) have been recently identified as a new class of potent non-nucleoside HIV-1 Reverse Transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses, has been used to elucidate the atomic details of the RT/TC interactions and to identify the most important features impacting the TC antiretroviral activity. The CoMFA model resulted to be the more predictive, and gave r(2)=0.93, r(cv)(2)=0.53, SEE=0.292, F=180, and r(test)(2)=0.70. The 3D-QSAR field contributions and the structural features of the RT binding site showed a good correlation. These studies will be useful to design new TCs with improved potency also against clinically relevant resistant mutants.