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

Acylthiocarbamates (ATCs) have been identified as a class of potent non-nucleoside HIV-1 reverse transcriptase (RT) inhibitors. A computational strategy based on molecular docking studies followed by comparative molecular fields analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) was used to identify the most important features impacting ATC antiretroviral activity. The CoMSIA model proved to be the more predictive, with r(2)(ncv) = 0.89, r(cv)(2) = 0.38, standard error of estimate (SEE) = 0.494, F = 84, and r(2)(pred) = 0.81. The results of these studies will be useful in designing new ATCs with improved potency, also against clinically relevant resistant mutants.