Research Articles

2019  |  Vol: 5(1)  |  Issue: 1(January-February)  |  https://doi.org/10.31024/ajpp.2019.5.1.18
Molecular docking assessment of N-heteroaryl substituted benzamide derivatives as glucokinase activators

Ajmer Singh Grewal1, 2*, Rajeev Kharb3, Jagdeep Singh Dua4, Viney Lather3

1Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India

2I. K. Gujral Punjab Technical University, Jalandhar, 144601, Punjab, India

3Amity Institute of Pharmacy, Amity University, Noida, 201303, U.P., India

4Shivalik College of Pharmacy, Naya-Nangal, 140126, Punjab, India

*Address for Correspondence

Ajmer Singh Grewal,

Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India

Abstract

Objective: Glucokinase (GK) activators are newer emerging class of therapeutic candidates, which activate GK in pancreatic β-cells and liver hepatocytes and show their hypoglycemic activity. The maximum drug discovery and development programmes linked to GK activators were primarily centered on the N-heteroaryl substituted benzamide derivatives. The present work was planned to predict the binding mode of a series of N-heteroaryl benzamide derivatives in the allosteric site of GK enzyme in a way to design newer GK activators. Material and Methods: A series of N-heteroaryl benzamide derivatives with reported high GK activity from literature were selected for the molecular docking studies. In silico molecular docking studies were performed for the selected derivatives in the allosteric binding site of GK protein using AutoDock Vina. Results: The superimpose of the docked poses of the selected benzamide derivatives with the GK-reference activator complex showed that the selected derivatives have the analogous binding pattern with the allosteric site residues of the enzyme as that of reference ligand. The results of the docking studies indicated that the amide group of the benzamide is required for the H-bonding interactions with Arg63 residue of GK protein and the aromatic rings are essential for the hydrophobic interactions with the residues in hydrophobic pocket in allosteric site of the GK protein. Conclusion: This information can be utilized to design novel potent, safe and effective GK activators based on benzamide scaffold for type 2 diabetes therapeutics.

Keywords: AutoDock, Benzamides, Docking, Glucokinase, GK activators, Type 2 diabetes

Manuscript Management System
Submit Article Subscribe Most Popular Articles Join as Reviewer Email Alerts Open Access
Our Another Journal
Another Journal
Call for Paper in Special Issue on

Call for Paper in Special Issue on