Combination of 2D and 3D-QSAR studies on DAPY and DANA derivatives as potent HIV-1 NNRTIs

Abstract

With the increasing patients suffered from AIDS, highly active antiretroviral therapy is considered as the most effective way to control this disease, leading to an urgent need for new potent drug discovery. Recently, a series of NNRTIs belonging to DAPY and DANA family was reported as promising anti-HIV agents. The CoMFA and CoMSIA analysis were conducted to build up 3D-QSAR models with satisfactory statistical parameters (q2 = 0.887 and R2 = 0.988 for CoMFA model, q2 = 0.901 and R2 = 0.990 for the optimal CoMSIA model). In order to perform further validation of the 3D-QSAR models, a SMILES-based software CORAL was applied to build up the 2D-QSAR model, which also provided essential structural information for further modifications. All three models showed excellent predictability. Combination of analysis of 3D contour maps derived from CoMFA and CoMSIA models and analysis of 2D molecular fragments derived from CORAL software gave insights into the design of novel anti-HIV agents.