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

被引：5
作者：
Gao, Mei [1 ,2 ]
Ma, Hui [2 ]
Liu, Xiaoyu [2 ]
Zhang, Yanhua [2 ]
Tang, Liansheng [2 ]
Zheng, Zhiyong [2 ]
Zhang, Xinlei [3 ]
Jiang, Chengshi [4 ]
Lin, Lin [2 ]
Sun, Haiji [1 ]
机构：
[1] Shandong Normal Univ, Coll Life Sci, Shandong Prov Key Lab Anim Resistance Biol, Jinan 250014, Peoples R China
[2] Shandong Acad Pharmaceut Sci, Jinan 250101, Peoples R China
[3] Fourth Mil Med Univ, Sch Pharm, Dept Med Chem, Xian 710032, Shaanxi, Peoples R China
[4] Univ Jinan, Sch Biol Sci & Technol, Jinan 250022, Peoples R China
来源：
CHEMISTRY & BIODIVERSITY | 2023年 / 20卷 / 02期
关键词：
oleanolic acid; pyrazole derivatives; alpha-glucosidase inhibitor; alpha-amylase; molecular docking; TYPE-2; DIABETES-MELLITUS; THERAPY; MECHANISM;
D O I：
10.1002/cbdv.202201178
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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.
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页数：9
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