In silico evaluation of N-methyl-1-adamantaneacetamide and 3′,4′-di-O-methyl ellagic acid-4α-La-rhamnopyranoside from Asystasia gangetica and Synadenium glaucescens pax as potential antidiabetic agents

Type 2 diabetes mellitus (T2DM) remains a worldwide health issue, requiring the development of new therapeutic agents with better effectiveness and safety. Plant-based compounds show promising potential, and computational methods allow efficient evaluation of their pharmacological properties. This study used molecular docking, ADME prediction, and molecular dynamics simulations to assess secondary metabolites from Asystasia gangetica and Synadenium glaucescens pax against important diabetic targets, including PPARγ, 11β-HS1, DPP4, and SGLT2. In silico analysis of secondary metabolites from A. gangetica and S. glaucescens pax identified 15 compounds likely to interact with selected proteins involved in blood sugar regulation. N-methyl-1-adamantaneacetamide and benzyl β-D-glucopyranoside demonstrated favourable ADME properties and showed strong binding energies. The highest binding energy observed was – 182.32 ± 11.49 kJ/mol with 3′,4′-di-O-methyl ellagic acid-4α-L-rhamnopyranoside in the PPAR system. Additionally, despite its robust van der Waals and electrostatic interactions, the considerable positive polar solvation energy notably affected the overall binding energy of 3′,4′-di-O-methyl ellagic acid-4α-L-rhamnopyranoside. Conversely, the lower polar solvation energy of N-methyl-1-adamantaneacetamide improved its overall binding energy, making it the ligand with the most favourable total binding energy within the PPAR system. The in-silico analysis indicates that N-methyl-1-adamantaneacetamide from Asystasia gangetica and 3′,4′-di-O-methyl ellagic acid-4α-L-rhamnopyranoside from Synadenium glaucescens are promising multi-target compounds for blood sugar regulation. Molecular dynamics simulations favour N-methyl-1-adamantaneacetamide for the Pparγ receptor and 3′,4′-di-O-methyl ellagic acid-4α-L-rhamnopyranoside for the SGLT2 receptor as the most effective ligands owing to their optimal binding properties and stability. Further experimental validation is necessary to evaluate their potential efficacy as antidiabetic drugs in vitro and in vivo.