QSAR BASED ON MULTIPLE LINEAR-REGRESSION AND PLS METHODS FOR THE ANTI-HIV ACTIVITY OF A LARGE GROUP OF HEPT DERIVATIVES

Quantitative structure-activity relationships have been developed for a set of 107 inhibitors of the HIV-1 reverse transcriptase, derivative s of a recently reported HIV-1 specific read: 1-[(2-hydroxyethoxy)meth yl]-6-(phenylthio)thymine (HEPT). The activity of these compounds was investigated by means of multiple linear regression (MLR) and PLS regr ession techniques and topological indexes as well as several tabulated physicochemical substituent constants were used as predictor variable s. The results obtained indicate that the anti-HIV activity of the HEP T derivatives is strongly dependent on hydrophobic factors as expresse d by the Hansch constant (Sigma pi(R1+R2)), and especially dependent o n the geometric factors mainly accounted for by the (1) chi(N)(R2) and (4) chi(p)(N) molecular connectivity indexes and also for the molecul ar volume (Vx), the Taft steric constant (Es(2R1)), and the Verloop pa rameter for the smallest width value (B1(3R1)). Besides, for this data set, comparison of the quality of MLR and PLS models show that PLS is a better approach to MLR for improving the interpretability of the da ta and also to exhibit models with a better predictive quality.