QSAR analysis on benzodithiazine derivatives as HIV-1 integrase inhibitors

Objective : Inhibition of HIV-1 integrase is an important strategy for the treatment of HIV and AIDS. Therefore, HIV-1 integrase inhibitory activity of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines has been analyzed with different physicochemical parameters. Methods : In the present work, quantitative structure activity relationship studies were performed on a series of benzodithiazines as HIV-1. integrase inhibitors using the modeling software Win CAChe version 6.1. Multiple linear regression analysis was performed to derive quantitative structure activity relationship models which were further evaluated for statistical significance and predictive power by internal and external validation. Results : The best QSAR. models were having good correlation coefficient (r) with low Standard error of estimation (SEE) and cross validated square of correlation coefficient (q(2)). The robustness of the models was checked by Y-randomization test and they were identified as good predictive models. The model for HIV integrase (wt) inhibitory activity of benzodithiazines suggest that the increase of dipole moment (Z) of molecules leads to reduce 3' processing and strand transfer inhibitory activity, substitution with high electro positive groups is conducive for the 3' processing inhibitory activity, and the increase in heat of formation is favorable for 3'-processing and strand transfer inhibitory activity. Conclusion The model for HIV integrase (C65s) inhibitory activity of benzodithiazines suggest that the increase of dipole moment (X) of molecules leads to reduce 3' processing and strand transfer inhibitory activity, and the substitution with high hydrophobic groups is conducive for the 3' processing and strand transfer inhibitory.