Exploring Quinoline Ring Derivatives as Potent Integrase Inhibitors Using Ligand-based Modeling Studies

Abstract

Integrase has become an attractive target for the design of anti-HIV inhibitor because it plays a quite important role in the process of HIV-1 virus replication. The quinoline ring derivatives, which have the similar pharmacophore to ..-diketoacids, are the kind of integrase inhibitor with highly antiviral activity. A series of quinoline ring derivatives were analyzed by the Comparative Molecular Field Analysis (CoMFA), comparative molecular similarity induces analysis (CoMSIA) and Topomer CoMFA methods. Firstly, we chose 77 compounds from former papers as a dataset, followed by dividing it into the training set and test set randomly. Then, we constructed predictive models of CoMFA, CoMSIA and Topomer CoMFA, respectively. The CoMFA yielded the best cross-validated model with a q²=0.758, non-cross-validated r²=0.988. The CoMSIA model yielded a q² =0.701 and r² =0.986 while the Topomer CoMFA model has q² =0.661 and r² = 0.966. Through verification, these results suggested a strong predictive ability to the design of novel highly active HIV-1 integrase inhibitors for therapy.