Discovery of lignans and curcuminoids as the effective inhibitors of pancreatic lipase: structure-activity relationship and inhibitory mechanism

Pancreatic lipase (PL) is the main enzyme in the digestive system that breaks down triglyceride and promotes its absorption. In this paper, we found that lignans <b>2</b>, <b>3</b> and <b>21</b>, curcuminoids <b>24-26</b> exhibited significant inhibitory potential against PL. The structure-activity relationship (SAR) indicated that benzo-1, 3-dioxole group in the construction of lignans is essential to inhibitory effects against PL, while double bonds at C-7/C-2 position and 4-hydroxyphenyl moiety in the structure of curcuminoids are beneficial for PL inhibition. The kinetic studies and molecular docking were also conducted, the results showed that the three curcuminoids with the strongest inhibition effect above were all mixed inhibitors of PL. Furthermore, curcuminoids <b>24-26</b> displayed a preferential selectivity towards, in contrast to other serine hydrolases. The above results indicate that lignans and curcuminoids are natural functional components for PL inhibition, providing new ideas for finding and developing novel lead compounds for the treatment of obesity.