Background: The development of severe drug resistance caused by the extensive use of
anti-HIV agents has resulted in a greatly extensive reduction in these drugs efficacy.
Objectives: To identify the important pharmacophoric features and correlate 3D chemical structure
of benzothiazinimines with their anti-HIV potential using 2D, 3D-QSAR and pharmacophore
Methods: QSAR and pharmacophore mapping studies have been used to relate structural features.
2D QSAR and 3D QSAR studies were performed using partial least square and k-nearest neighbor
methodology, coupled with various feature selection methods, viz. stepwise, genetic algorithm,
and simulated annealing, to derive QSAR models which were further validated for statistical significance.
Results: The physicochemical descriptor XAHydrophilicArea and SsOHE-index, and alignmentindependent
descriptor T_C_Cl_6 showed significant correlation with the anti-HIV activity of
benzothiazinimines in 2D QSAR. 3D QSAR results showed the significant effect of electrostatic
and steric field descriptors in the anti-HIV potential of benzothiazinimines. The generated pharmacophore
hypothesis demonstrated the importance of aromaticity and hydrogen bond acceptors.
Conclusion: The significant models obtained in this study suggested that these techniques could
be used as a guidance for designing new benzothiazinimines with enhanced anti-HIV potential.