Kumar_2025_Chem.Biodivers__e202403368

The distinguishing characteristic of diabetes mellitus (DM), chronic hyperglycemia emphasizes the need of safer, more efficient antidiabetic treatments. This study employs computational approaches to explore the therapeutic potential of phytochemicals from medicinal plants as antidiabetic drugs. Molecular docking against phosphorylated insulin receptor (IR) tyrosine kinase and human dipeptidyl peptidase IV (DPP-IV) identified eriodictyol (-7.13 kcal/mol) and petunidin (-6.61 kcal/mol) as potent inhibitors. Molecular dynamics (MD) simulations confirmed the structural stability of these complexes, with root mean square deviation (RMSD) values stabilizing within 2.8-4.5 A. Binding free energy calculations using Molecular Mechanics Generalized Born Surface Area (MM-GBSA) revealed strong binding affinities of eriodictyol-IR (deltaG binding=-44.63+/-4.05 kcal/mol), and petunidin-DPP-IV complex (deltaG binding=-49.86+/-6.13 kcal/mol). Additionally, pharmacokinetic assessments showed that these compounds adhered to Lipinski's rule, with no significant hepatotoxicity or cytotoxicity. These findings underscore the potential of these phytocompounds as antidiabetic candidates, warranting further in vitro and in vivo investigations.