Anti-diabetic drug discovery using the bioactive compounds of Momordica charantia by molecular docking and molecular dynamics analysis

Diabetes mellitus (DM) is a multifactorial life-threatening endocrine disease characterized by abnormalities in glucose metabolism. It is a chronic metabolic disease that involves multiple enzymes such as α-amylase and α-glucosidases. Inhibition of these enzymes has been identified as a promising method for managing diabetes, and researchers are currently focusing on discovering novel α-amylase and α-glucosidase inhibitors for diabetes therapy. Hence, we have selected 12 bioactive compounds from the Momordica charantia (MC) plant and performed a virtual screening and molecular dynamics investigation to identify natural inhibitors of α-amylase and α-glucosidases. Our in silico result revealed that phytocompound Rutin showed the highest binding affinity against α-amylase (1HNY) enzymes at (−11.68 kcal/mol), followed by Karaviloside II (−9.39), Momordicoside F (−9.19), Campesterol (−9.11. While docking against α-glucosidases (4J5T), Rutin again showed the greatest binding affinity (−11.93 kcal/mol), followed by Momordicine (−9.89), and Campesterol (−8.99). Molecular dynamics (MD) simulation research is currently the gold standard for drug design and discovery. Consequently, we conducted simulations of 100 nanoseconds (ns) to assess the stability of protein-ligand complexes based on parameters like RMSD, RMSF, RG, PCA, and FEL. The significance of our findings indicates that rutin from MC might serve as an effective natural therapeutic agent for diabetes management due to its strongest binding affinities with α-amylase and α-glucosidase enzymes. Further research in animals and humans is essential to validate the efficacy of these drug molecules.