Neural Networks:  Accurate Nonlinear QSAR Model for HEPT Derivatives

Abstract

A nonlinear quantitative structure-anti-HIV-1-activity relationship (QSAR) study was investigated in a series of 1-[2-hydroxyethoxy-methyl]-6-(phenylthio) thymine] (HEPT) derivatives acting as nonnucleoside reverse transcriptase inhibitors (NNRTIs). This QSAR study has been undertaken by a three-layered neural network (NN) using molecular descriptors known to be responsible for the anti-HIV-1 activity. The usefulness of the model and the nonlinearity of the relationship between molecular descriptors and anti-HIV-1 activity have been clearly demonstrated. The obtained model outperforms those given in the literature in both the fitting and predictive stages. NN analysis yielded predicted activities in excellent agreement with the experimentally obtained values (R(2) = 0.977, predictive r(2) = 0.862). The effect of each molecular feature on the anti-HIV-1 activity variation has been clearly elucidated.