QSAR and Pharmacophore Mapping Studies on Benzothiazinimines to Relate their Structural Features with anti-HIV Activity

Title:QSAR and Pharmacophore Mapping Studies on Benzothiazinimines to Relate their Structural Features with anti-HIV Activity

Volume: 14 Issue: 7

Author(s): Gopiraja Geethaavacini, Go Poh Poh, Lim Yi Yan, Rajindran Deepashini , Sivadasan Shalini, Rajak Harish, Krishnan Sureshkumar and Veerasamy Ravichandran*

Affiliation:

• Faculty of Pharmacy, AIMST University, Semeling – 08100, Kedah,Malaysia

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

Abstract: 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.

Cite this article as:

Geethaavacini Gopiraja , Poh Poh Go , Yan Yi Lim , Deepashini Rajindran , Shalini Sivadasan , Harish Rajak , Sureshkumar Krishnan and Ravichandran Veerasamy*, QSAR and Pharmacophore Mapping Studies on Benzothiazinimines to Relate their Structural Features with anti-HIV Activity, Medicinal Chemistry 2018; 14 (7) . https://dx.doi.org/10.2174/1573406414666180529091618