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 modeling studies.
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.
Keywords: 2D QSAR, 3D QSAR, benzothiazinimines, pharmacophore mapping, anti-HIV, AIDS.