QSAR study and molecular docking of benzimidazole derivatives as potent activators of AMP-activated protein kinase

3D-QSAR and molecular docking methods were performed on a set of 74 benzimidazole derivatives previously studied as activators of the AMP-activated protein kinase (AMPK), a protein that plays a key role in the regulation of cellular energy balance. Relative enzyme activity (REA) of 74 compounds was quantitatively modelled using multiple linear regression (MLR) and neuronal networks (NN). The proposed QSAR model provided statistically significant results (rMLR = 0.89; rNN = 0.95 and rCV = 0.90) and was validated using the leave-one-out method. The general binding mode of benzimidazole derivatives to the AMPK binding site was explored using molecular docking, with a focus on the most active molecules of our set, compounds 19 and 25.