Comparative computational analysis of the antidiabetic potential of momordenol, momordicilin, charantin and vicine from Momordica charantia (bitter melon)

Momordica charantia, a widely recognized medicinal plant in Eastern (Ayurvedic) medicine, is celebrated for its phytochemical constituents, which have demonstrated significant antidiabetic potential by effectively lowering blood glucose levels in diabetic patients. This study aimed to provide a comparative analysis of the antidiabetic potential of four bioactive compounds: momordenol, momordicilin, charantin, and vicine from Momordica charantia, relative to the reference compound, N-(4-methoxybenzyl)-N’-(5-nitro-1,3-thiazol-2-yl) urea (TUM). Molecular docking simulations revealed that momordenol exhibited the highest binding affinity as a potential natural antidiabetic agent, inhibiting the key enzyme glycogen synthase kinase-3 (GSK-3) with a docking score of -9.91 kcal/mol. Momordenol adhered to Lipinski’s Rule of Five with minimal violations, suggesting its viability as an oral drug candidate. In silico ADMET analysis showed that both momordicilin and momordenol achieved superior intestinal absorption rates of 96.55% and 95.77%, respectively, compared to TUM’s absorption rate of 84.38%, indicating enhanced oral bioavailability. Among the four compounds, momordicilin demonstrated the highest volume of distribution (VDss), indicating its broad systemic distribution, whereas momordenol and charantin were more localized in their distribution profiles. Toxicity assessment using ProTox 3.0 classified charantin in toxicity class 6, based on its LD₅₀ value of 8000 mg/kg, suggesting its safety as a potential antidiabetic therapeutic. In contrast, momordenol and momordicilin exhibited moderate toxicity, yet they remain promising candidates for further pharmacological development.