STRUCTURE-ACTIVITY CORRELATION STUDY OF HIV-1 INHIBITORS - ELECTRONICAND MOLECULAR-PARAMETERS

Quantitative structure-activity relationships (QSARs) for 40 HIV-1 inh ibitors, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine and its der ivatives, were studied. Fully optimized geometries, based on the semie mpirical AMI method, were used to calculate electronic and molecular p roperties of all compounds. In order to examine the relation between b iological activities and structural properties, multiple linear regres sion models were employed. A suitable QSAR model was obtained, showing not only statistical significance, but also predictive ability. The s ignificant molecular descriptors used were atomic charges of two subst ituted carbon atoms in the thymine ring, hydration energies and molar refractivities of the molecules. These descriptors allowed a physical explanation of electronic and molecular properties contributing to HIV -I inhibitory potency.