Identification of new antidiabetic agents targeting GLUT4 protein using in silico analysis

Abstract

Objective: Diabetes mellitus is a metabolic syndrome that constitutes a major health problem. It is estimated that 246 million people worldwide have diabetes and that 380 million people will be afflicted with diabetes by 2025. In addition, 3.8 million people die each year from diabetes. Natural products offer an advanced starting point in the search for highly specific and potent modulators of bimolecular function as well as novel drugs. In the present study, GLUT4 protein which plays a significant role in protecting β-cells from damage was selected as potential target. Materials and Methods: Three-dimensional structure of GLUT4 protein was build using modeller9v9.19. Modeled structure was validated through structure analysis verification server. With the purpose of identifying, the new potential drugs against GLUT4 protein molecular docking studies of 20 natural compounds were carried out using AutoDock. Results: The modeled structure has 87.9% residues in the core region. Results of docking studies clearly showed that good binding interactions of the ligand with both the targets at very low energy level. Conclusion: Based on the docking energy value, H-bond interaction the compounds hesperidin, fisetin, eriodictyol, wogonin, and chrysin was selected as the most potent compounds for GLUT4 protein. Hence, this present study suggests the consideration of these compounds for further in vitro and in vivo studies for its development as antidiabetic drugs.