Molecular Docking Analysis of Flavonoids from Verbascum Species Against Key Antidiabetic Targets: α-Glucosidase and Dipeptidyl Peptidase-IV (DPP-IV)

Diabetes is one of the most significant global health challenges. With synthetic drugs causing side effects, researchers are turning to natural alternatives for prevention and treatment. This study used molecular docking to predict the interaction of flavonoids from Verbascum spp. and their affinity for binding to α-glucosidase (3WY1) and DPP-IV (5J3J) enzymes. Binding energies, hydrogen bond interactions, and hydrophobic contacts at the active sites were analyzed. Kaempferide stood out against α-glucosidase with the lowest binding energy (‒5.03 kcal/mol), forming strong hydrogen bonds to GLU231 (1.70 Å), LEU300 (1.95 Å), and ASN301 (2.00 Å). Luteolin 7-O-β-D-glucopyranoside showed weaker binding (‒3.37 kcal/mol) with bonds to GLU383 (1.88, 2.29 Å) and TRP394 (2.45 Å). For DPP-IV, luteolin had the best affinity (‒6.01 kcal/mol), creating five hydrogen bonds with GLY335 (1.92, 2.11 Å), SER277 (2.08 Å), TRP337 (2.82 Å), and SER275 (2.99 Å). These results position kaempferide and luteolin as promising candidates for developing natural antidiabetic agents from Verbascum species.