Pharmacophore modeling of some novel indole β-diketo acid and coumarin-based derivatives as HIV integrase inhibitors

Abstract

To design new chemotypes with enhanced potencies against the HIV integrase enzyme, 3D pharmacophore models were generated and QSAR study was carried out on 44 novel indole β-diketo acid derivatives and coumarin-based Inhibitors. A five-point pharmacophore with two hydrogen bond acceptors (A) and three aromatic rings (R) as pharmacophore features was developed by PHASE module of Schrodinger suite. The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of R2 = 0.81 for training set compounds. The model generated showed excellent predictive power, with a correlation coefficient of Q2 = 0.69 for a randomly chosen test set of eight compounds. The 3D-QSAR plots illustrated insights into the structure activity relationship of these compounds which may helps in the design and development of novel integrase inhibitors.