Inhibition of human pancreatic lipase, a crucial enzyme in dietary fat digestion and absorption, is a potent therapeutic approach for obesity treatment. In this study, human pancreatic lipase inhibitory activity of aurone derivatives was explored by molecular modeling approaches. The target protein was human pancreatic lipase (PDB ID: 1LPB). The 3D structures of 82 published bioactive aurone derivatives were docked successfully into the protein catalytic active site, using AutoDock Vina 1.5.7.rc1. Of them, 62 compounds interacted with the key residues of catalytic trial Ser152-Asp176-His263. The top hit compound (A14), with a docking score of −10.6 kcal⋅mol⁻¹, was subsequently submitted to molecular dynamics simulations, using GROMACS 2018.01. Molecular dynamics simulation results showed that A14 formed a stable complex with 1LPB protein via hydrogen bonds with important residues in regulating enzyme activity (Ser152 and Phe77). Compound A14 showed high potency for further studies, such as the synthesis, in vitro and in vivo tests for pancreatic lipase inhibitory activity.

In this study, 82 aurone compounds, a subclass of flavonoids were investigated towards to human pancreatic lipase inhibitory activity. Molecular docking of the aurones was done successfully into the catalytic position of lipase (Pdb: 1LPB) using AutoDock Vina software 1.5.7.rc1. The results showed that 62 compounds interacted well with residues in the catalytic trial Ser152-Asp176-His263 and Phe77 of protein 1LPB. In particular, A32 was selected as the best binding compound (docking score: -10.6 kcal.mol-1) and suitable for oral drug following the 5-Lipinski rule. Combining the results of docking and molecular dynamics simulation of A32- protein complex during 10 ns, this study performed that the A32 compound bound well and formed a stable complex with 1LPB protein. Therefore, the A32 compound was considered as the lead compound which could be synthesized and tested for pancreatic lipase inhibitor.