Bayrak_2026_ChemistryOpen_15_e70227

Lipase inhibition is a key strategy for controlling dietary fat absorption and managing obesity. In this study, lipase produced from Bacillus licheniformis LP-8 (GenBank accession number: PX970421), using waste frying oil, was used to evaluate the inhibitory potential of selected flavonoid compounds. In vitro inhibition assays revealed IC(50) values ranging from 1.28 to 3.51 microM, with syringetin exhibiting the strongest inhibitory activity (IC(50) = 1.28 +/- 0.009 microM), surpassing the reference inhibitor, orlistat (IC(50) = 2.13 +/- 0.010 microM). Structure-activity relationship analysis indicated that electron-donating substituents, particularly methoxy and hydroxyl groups on the B-ring, play a crucial role in enhancing lipase inhibition. To further elucidate the interaction mechanisms, molecular docking and molecular dynamics (MD) simulations were performed. Induced Fit Docking results demonstrated favorable binding affinities for syringetin, diosmin, and isorhamnetin-3-O-rutinoside, with syringetin showing the most stable binding profile. Subsequent 250 ns MD simulations confirmed the structural stability of the lipase-syringetin complex through persistent hydrogen bonding and Pi-Pi interactions, indicating a well-oriented and stable binding mode. Overall, the combined experimental and computational findings highlight the potential of flavonoids, particularly syringetin, as promising natural lipase inhibitors for obesity-related applications.