Interaction analysis of quinolone alkaloids derived from Euodia fruit with human pancreatic lipase through docking simulation

¹ Tokyo University of Pharmacy and Life Science, School of Life Science, Japan
² The Institute of Statistical Mathematics, Japan
³ Tokyo University of Pharmacy and Life Science, School of Pharmacy, Japan
⁴ Tokyo Woman’s Christian University, Japan

Abstract

Obesity is associated with various metabolic disorders, and pancreatic lipase inhibitors are important therapeutic agents that suppress fat absorption. Quinolone alkaloids isolated from Euodia fruit have been reported to exhibit inhibitory activity against pancreatic lipase. In this study, docking simulations were performed using 33 ligands, including 14 isolated quinolone alkaloids and 19 virtual stereoisomers, against human pancreatic lipase. The ligands were classified into three structural groups based on carbon chain saturation and the presence of hydroxyl groups, and their docking results were compared with experimental activity. Overall, the docking results were consistent with the experimental data, showing positive correlations between structural groups 1 and 3. Notably, Mol 10, which interacted with His151, exhibited a high docking score despite its low experimental activity, whereas Mol 14-1, which interacted with His263, demonstrated strong inhibitory activity and a positive correlation with the docking scores. These findings suggest that the docking score may not always strongly correlate with experimental potency, as it can depend on the docking pose. This study highlights the potential of quinolone alkaloids as pancreatic lipase inhibitors and emphasizes the importance of analyzing ligand-residue interactions.