Computational analysis of potential drug-like compounds from Solanum torvum - A promising phytotherapeutics approach for the treatment of diabetes

Abstract

Diabetes mellitus (DM) is a global pandemic that is characterized by high blood glucose levels. Conventional treatments have limitations, leading to the search for natural alternatives. This study focused on Solanum torvum (STV), a medicinal plant, to identify potential anti-diabetic compounds using molecular docking and molecular dynamics simulations. We focused on identifying natural inhibitors of two key enzymes involved in glucose metabolism: α-amylase (1HNY) and α-glucosidase (4J5T). In our preliminary docking study, rutin showed the highest binding affinity (−11.58 kcal/mol) to α-amylase, followed by chlorogenin (−7.58 kcal/mol) and myricetin (−5.82 kcal/mol). For α-glucosidase, rutin had the highest binding affinity (−11.78 kcal/mol), followed by chlorogenin (−7.11 kcal/mol) and fisetin (−6.44 kcal/mol). Hence, chlorogenin and rutin were selected for further analysis and compared with acarbose, an FDA-approved antidiabetic drug. Comparative docking revealed that chlorogenin had the highest binding affinity of (−9.9 kcal/mol) > rutin (−8.7 kcal/mol) and > acarbose (−7.7 kcal/mol) for α-amylase. While docking with α-glucosidase, chlorogenin again had the highest binding affinity of (−9.8 kcal/mol) > compared to rutin (−9.5 kcal/mol) and acarbose (−7.9 kcal/mol). Molecular dynamics (MD) simulations were conducted to assess their stability. We simulated 100 nanoseconds (ns) trajectories to analyze their stability on various parameters, including RMSD, RMSF, RG, SASA, H-bond analysis, PCA, FEL, and MM-PBSA on the six docked proteins. In conclusion, our study suggests that chlorogenin and rutin derived from STV may be effective natural therapeutic agents for diabetes management because of their strong binding affinities for the α-amylase and α-glucosidase enzymes. Communicated by Ramaswamy H. Sarma