α-Glucosidase Enzyme Inhibitors from Shorea beccariana, Pharmacokinetic and Mechanism Insights through In vitro and In silico Studies

A bioassay-guided phytochemical investigation of the endangered plant Shorea beccariana led to the isolation of two bioactive compounds: 3-O-methylellagic acid 3'-O--rhamnoside (EAG) and Bergenin (BER).Their structures were elucidated using a combination of 1D and 2D NMR spectroscopy, UV-Vis spectrophotometry, and FTIR analysis.The pharmacokinetic profiles of both compounds were evaluated through in silico ADMET, bioavailability, and drug-likeness assessments, indicating favorable drug-like properties.In vitro -glucosidase inhibitory activity assays revealed that EAG (IC = 562.4 0.11 M) was slightly more potent than the reference inhibitor acarbose (IC = 619.8 0.03 M), while BER (IC = 1127.6 0.09 M) demonstrated a weaker inhibition.To further elucidate their mechanisms of action, molecular docking and molecular dynamics (MD) simulations were performed.Binding free energies (G_bind), calculated via the QM/MM-GBSA method, revealed strong interactions with -glucosidase: EAG (-40.76 kcal/mol), BER (-34.53 kcal/mol), and acarbose (-33.86 kcal/mol).Notably, although BER was less potent than acarbose in vitro, its superior binding affinity in silico suggests potential benefits from molecular flexibility and dynamic stabilization.