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

Quantitative structure-activity relationships (QSAR) and Comparative Molecu lar Field Analysis (CoMFA) have been applied in order to explain the struct ural requirements of HIV-1 reverse transcriptase (HIV-1 RT) inhibitory acti vity of TIBO derivatives on the MT-4 cells. The best QSAR model is satisfac tory in both statistical significance and predictive ability. The derived s tructural descriptors indicate the importance of electronic contributions t oward 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 cor relation, 3D-QSAR was performed using CoMFA. The obtained CoMFA model shows high predictive ability, r(cv)(2)=0.771, and clearly demonstrates its pote ntial in the steric feature of the molecules through contour maps, explaini ng a majority (81.8%) of the variance in the data. Consequently, these resu lts can be useful in identifying the structural requirements of TIBO deriva tives and helpful for better understanding the HIV-1 RT inhibition. Eventua lly, they provide a beneficial basis to design new and more potent inhibito rs of HIV-1 RT.