Combined Pharmacophore Modeling, 3D-QSAR, Molecular Docking and Molecular Dynamics Study on Indolyl-aryl-sulfone Derivatives as New HIV1 Inhibitors.

The present study deals with the in silico of 45 indolyl-aryl-sulfones known as anti-HIV1. The data were collected from recent previously reported inhibitors and divided into a sub-set of 33 compounds as the training set and the remaining 12 compounds were kept in the test set. The selected pharmacophore-ADRRR-yielded a statistically significant 3D-QSAR model containing high confidence scores (R2 = 0.930, Q2 = 0.848, and RMSE = 0.460). The predictive power of the established pharmacophore model was validated with an external test (r2 = 0.848). A systematic virtual screening workflow shows an enrichment factor and has revealed a high predictive power. Then the model was used to screen the filtered PubChem database mapping all chemical features of model pharmacophore. The recognized hits were further assessed by in silico ADMET studies. Molecular dynamics also used to explore the stability of obtained complexes. Finally, these selected compounds are probably to become a good lead molecule for the development of effective anti-HIV-1 drugs.