Harnessing the therapeutic potential of Coccinia grandis phytochemicals in diabetes: A computational, DFT calculation and MMGBSA perspective on aldose reductase inhibition

Abstract

The role of aldose reductase (ALR), the key enzyme of the polyol pathway, has been firmly established in hyperglycemia-induced diabetic complications. Therefore, the present study focused on the screening of phytochemicals reported in Coccinia grandis against ALR using in-silico methodologies encompassing molecular docking, pharmacokinetics, molecular dynamic simulation, free energy calculation (MMGBSA), and quantum mechanics. A comprehensive array of 101 compounds from C. grandis documented in IMPPAT database and different literatures have been selected in this study. These compounds were meticulously docked with the ALR (PDB ID: 1EL3), yielding docking scores spanning a range of −5.8 to −11.0 kcal/mol compared to the positive control epalrestat with a score of −7.9kcal/mol. Among them, four compounds have been emerged as the most promising ALR inhibitors: tiliroside, lukianol B, formononetin, and trachelogenin, with docking scores of −11.0, −10.7, −10.4, and −10.2, respectively. Importantly, these compounds exhibited notable stability throughout 100 ns dynamic simulations compared to the control drug, aligning with Lipinski's rule of 5, standard ADME properties, and evincing an absence of anomalous toxic effects. Therefore, these compounds hold great promise as leads to the development of potent ALR inhibitors; however, further studies are needed to warrant their uses in ameliorating diabetic complications.