Design synthesis and Biological Evaluation of Ndvel Quinoxaline Derivatives Targeted to HIV-1GP120

Abstract

HIV-1 gp120 enzyme, have been recognized as one of the prospective therapeutic targets for the treatment of AIDS. Nevertheless, the functional penalties of gp120 continue to be incompletely determined because of the binding approaches of gp120. In course of this research work to design novel gp120 inhibitors, computational approach was used. Pharmacophore model was generated using 7 structurally diverse molecules using GALAHAD module of Sybyl. Model 36 containing 9 features; four acceptor atom, one donor atom and four hydrophobic region had highest fitness score and best validation results. Hence best model, model 36 was used as a query for virtual screening in NCI database and 5 compounds with Qfit value ≥ 70 were retrieved. 3D-QSAR was carried on tweentynine, phenylcarbxamide derivatives. Contour map analysis of best CoMFA and CoMSIA model suggested that by substituting hydrophobic, bulky and electronegative groups, potency of the compound could be improved. The quinoxaline ring which is bio- isostere of quinoline ring, retrieved as hit in virtual screening, was selected as a core moiety. Designed quinoxaline derivatives were docked into active site of gp120 structure complex and In-Silico ADMET properties were also predicted. Synthesis of top 12 quinoxaline derivatives was carried out and spectral characterization was carried out using Mass, 1H and 13C-NMR spectroscopy.