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

Abstract A series of novel substituted pyrazole‐fused oleanolic acid derivative were synthesized and evaluated as selective α‐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 α‐glucosidase over α‐amylase. Analog 4d showed potent inhibitory activity against α‐glucosidase (IC 50 =2.64±0.13 μM), and greater selectivity towards α‐glucosidase than α‐amylase by ∼33‐fold. Inhibition kinetics showed that compound 4d was a non‐competitive α‐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.