Quantitative structure-activity relationships and comparative molecular field analysis of TIBO derivatised HIV-1 reverse transcriptase inhibitors.

Abstract

Quantitative structure-activity relationships (QSAR) and Comparative Molecular Field Analysis (CoMFA) have been applied in order to explain the structural requirements of HIV-1 reverse transcriptase (HIV-1 RT) inhibitory activity of TIBO derivatives on the MT-4 cells. The best QSAR model is satisfactory in both statistical significance and predictive ability. The derived structural descriptors indicate the importance of electronic contributions toward the HIV-1 RT inhibition of this class of compounds. However, it could not reveal any hydrophobic influence because of high collinearity between C2 and log P variables. In order to cope with steric interaction in the correlation, 3D-QSAR was performed using CoMFA. The obtained CoMFA model shows high predictive ability, rcv2 = 0.771, and clearly demonstrates its potential in the steric feature of the molecules through contour maps, explaining a majority (81.8%) of the variance in the data. Consequently, these results can be useful in identifying the structural requirements of TIBO derivatives and helpful for better understanding the HIV-1 RT inhibition. Eventually, they provide a beneficial basis to design new and more potent inhibitors of HIV-1 RT.