Synthesis of Echinocystic Acid Derivatives and Inhibitory Effect on Lipase / 中国实验方剂学杂志

ABSTRACT

Objective:Echinocystic acid(EA)is a kind of oleanolic pentacyclic triterpenoid compound,due to its main structural features of stability and less active sites,the structures of EA were modified in this paper to synthesize a series of EA derivatives, improve their bioavailability, and investigate their inhibitory effect on lipase. Method:In this study,EA derivatives were designed and synthesized from EA,which is a natural lipase inhibitor. Their inhibitory effects on lipase were tested by using 2,4-dinitrophenyl butanoate(PNPB) method. Result:Nine compounds were synthesized,and their structures were characterized by infrared spectrum (IR), ultraviolet spectrum (UV), mass spectrum (MS), nuclear magnetic resonance spectrum (1H-NMR and 13 C-NMR),all of which were identified as new compounds. Further experiments on the inhibitory effect on lipase showed that compounds 1-9 had higher inhibitory effects than EA,IC50=7.03,2.05,2.14,3.65,3.24,0.28,0.34,0.46,and 0.39 g·L-1. Compounds 6-9 had higher inhibitory effect than Orlistat(IC50=0.53 g·L-1). Inhibition rates were as follows6 > 7 > 9 > 8 > Orlistat> 2 > 3 > 5 > 4 > 1 >EA. Conclusion:It is feasible to design and synthesize derivatives with EA as the lead compound to improve the inhibitory effect on lipase.