Design of novel benzimidazole derivatives as potential α-amylase inhibitors by 3d-qsar modeling and molecular docking studies

Abstract

The enzyme α-amylase belongs to the highly conserved glycoside hydrolase family which is regarded as a good target for the discovery of antidiabetic agents. Following a 3D-QSAR study on forty-five 2-aryl benzimidazole derivatives which have been reported as potential insulin-independent antidiabetic agents. The results revealed that the CoMFA values were found to be 0.696 and 0.860 for Q2 and R2 respectively; while for the CoMSIA, the Q2 and R2 values were found to be 0.514 and 0.852 respectively. Both models were derived from a training set of thirty-seven compounds based on an appropriate method of alignment, while the predictive ability was approved by a test set containing eight compounds with rext 2 values of 0.990 and 0.987, respectively. Moreover, the contour maps generated from CoMFA and CoMSIA models provided much helpful information to figure out the structural requirements that influence the activity. To further reinforce the 3D-QSAR results, the molecular docking method was implemented which led to the design of new potential insulin-independent antidiabetic compounds with high predicted activity values.