Molecular Docking and In Vitro Assessment of Gymnema sylvestre R. Br. and Trigonella foenum‐graecum L. Phytochemicals as Dual α‐Amylase and α‐Glucosidase Inhibitors

ABSTRACT Gymnema sylvestre R. Br. (gurmar, Asclepiadaceae) and Trigonella foenum‐graecum L. (Fenugreek, Fabaceae) are medicinal plants with proven antidiabetic activity. This study employed the construction of a 221‐compound library from G. sylvestre and T. foenum‐graecum for virtual screening against α‐amylase and α‐glucosidase target proteins. It aimed to analyze phytochemical–target protein interactions via molecular dynamic simulations and validation of findings using in vitro antidiabetic assays. Bioinformatics tools facilitated virtual screening, molecular dynamics simulations, and ADMETox analysis. The α‐amylase and α‐glucosidase inhibitory potentials were screened in vitro using 50% EtOH extracts of G. sylvestre leaves and T. foenum‐graecum seeds with acarbose as the reference compound. Trigoneoside XIIa (−9.1 kcal/mol) and trigofoenoside G (−9.8 kcal/mol) derived from T. foenum‐graecum and gymnemasaponin V (−9.7 kcal/mol) derived from G. sylvestre showed the most stable binding interaction with the target proteins. In vitro assays further revealed that T. foenum‐graecum seed extract showed the highest α‐amylase inhibition (IC 50 = 12.09 ± 2.13 mg/mL) and α‐glucosidase inhibition (IC 50 = 5.23 ± 0.33 mg/mL). Trigoneoside XIIa, trigofoenoside G, and gymnemasaponin V were identified as promising drug candidates for the development of antidiabetic drug leads, further validating the in vitro α‐amylase and α‐glucosidase inhibitory potentials.