CoMFA and CoMSIA 3D QSAR and Docking Studies on Conformationally-Restrained Cinnamoyl HIV-1 Integrase Inhibitors: Exploration of a Binding Mode at the Active Site

摘要: Anti-HIV (human immunodeficiency virus) drug discovery has been increasingly focusing on HIV integrase (IN) as a potential therapeutic target. This enzyme is required for the integration of reverse transcribed proviral DNA into host cell's genome and essential propagation life cycle. Comparative molecular field analysis (CoMFA) comparative similarity indices (CoMSIA) three-dimensional quantitative structure−activity relationship (3D QSAR) studies docking simulations were conducted series potent conformationally restrained cinnamoyl inhibitors HIV-1 IN (Artico; et al. J. Med. Chem. 1998, 41, 3948−3960). Predictive 3D QSAR models established using SYBYL multifit alignment rule, which had conventional r2 cross-validated coeffiecient (q2) values up to 0.981 0.721 CoMFA 0.975 0.804 CoMSIA, respectively. These validated by an external test set (Burke; 1995, 38, 4171−4178). CoMF...