In silico molecular docking approach to investigate the anti-diabetic potential of natural, semi-synthetic, and synthetic compounds for diabetes management

Harshitha, V and Jose, Smitha and Dhanush, GS and Digvijaymandal, Digvijaymandal (2025) In silico molecular docking approach to investigate the anti-diabetic potential of natural, semi-synthetic, and synthetic compounds for diabetes management. World Journal of Biology Pharmacy and Health Sciences, 23 (2). pp. 301-314. ISSN 2582-5542

Oxidative stress plays a critical role in the pathogenesis of diabetes mellitus, and the nuclear factor erythroid 2 related factor 2 (Nrf2) pathway has emerged as a promising target for its regulation. Activation of Nrf2 enhances the transcription of antioxidant and cytoprotective genes, offering a novel therapeutic approach for managing diabetes. In silico molecular docking study, we employed molecular docking software to evaluate and compare the binding affinities of selected natural, semi-synthetic, and synthetic compounds against key Nrf2 pathway proteins, particularly the Keap1-Nrf2 interaction site. The compounds were docked to assess their potential to disrupt the Keap1-Nrf2 complex and thereby promote Nrf2 activation. The evaluated compounds possessed good docking scores and followed Lipinski Rule of 5, with additional pharmacokinetic predictions using SwissADME to evaluate binding energies, hydrogen bond formation, and the specific amino acid residues involved in the interactions. These findings support the role of both natural and synthetic molecules in modulating oxidative stress through the Nrf2 pathway. Further in vitro and in vivo studies are warranted to validate these results and explore their therapeutic applications in diabetes management.