Designing of Novel Potential Inhibitors of a-amylase by 3D-QSAR Modeling and Molecular Docking Studies

Abstract

The α-amylase is an enzyme of a highly conserved glycoside hydrolase family, α-amylase inhibitors can be used as clinical agents for the treatment of Diabetes Mellitus (DM). A 3D-QSAR study was performed on 45 2-aryl benzimidazole derivatives, which have been identified as insulin-independent antidiabetic agents. The 3D-QSAR technique includes CoMFA with Q2 of 0.696 and R2 of 0.860 and CoMSIA with Q2 of 0.514 and R2 of 0.852. Both models were derived from a training set of 37 compounds based on an appropriate method of alignment, while the predictive ability was approved by a test set containing 8 compounds with rext2 values of 0.990 and 0.987, respectively. Moreover, contour maps generated from CoMFA and CoMSIA models provided much helpful information to figure out the features requirements that have control over the activity. To further reinforce the 3D-QSAR results, the molecular docking method was implemented which led to design new potent insulin-independent antidiabetic compounds with high predicted activity values.