Synthesis and Biological Evaluation of Substituted Pyrazole-Fused Oleanolic Acid Derivatives as Novel Selective α-Glucosidase Inhibitors

A series of novel substituted pyrazole-fused oleanolic acid derivative were synthesized and evaluated as selective alpha-glucosidase inhibitors. Among these analogs, compounds 4a-4f exhibited more potent inhibitory activities compared with their methyl ester derivatives, and standard drugs acarbose and miglitol as well. Besides, all these analogs exhibited good selectivity towards alpha-glucosidase over alpha-amylase. Analog 4d showed potent inhibitory activity against alpha-glucosidase (IC50=2.64 & PLUSMN;0.13 mu M), and greater selectivity towards alpha-glucosidase than alpha-amylase by & SIM;33-fold. Inhibition kinetics showed that compound 4d was a non-competitive alpha-glucosidase inhibitor, which was consistent with the result of its simulation molecular docking. Moreover, the in vitro cytotoxicity of compounds 4a-4f towards hepatic LO2 and HepG2 cells was tested.