文献类型：期刊文献

英文题名：Synthesis of glucoconjugates of oleanolic acid as inhibitors of glycogen phosphorylase

作者：Cheng, Keguang[1,2];Liu, Jun[3];Liu, Xiaofeng[4];Li, Honglin[4,5];Sun, Hongbin[1];Xie, Juan[2]

机构：[1]China Pharmaceut Univ, Coll Pharm, Ctr Drug Discovery, Nanjing 210009, Peoples R China;[2]UniverSud, CNRS, ENS Cachan, PPSM, F-94230 Cachan, France;[3]China Pharmaceut Univ, Jiangsu Ctr Drug Screening, Nanjing 210038, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Drug Discovery & Design Ctr, Shanghai 201203, Peoples R China;[5]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2009

卷号：344

期号：7

起止页码：841

外文期刊名：CARBOHYDRATE RESEARCH

收录：;EI(收录号：20091812064490);WOS:【SCI-EXPANDED(收录号:WOS:000266192500001)】；

基金：K.C. thanks the French Embassy in China for a co-tutor Doctorate fellowship. This work is supported by a grant from Region Ile-de-France. H.S. thanks financial support by National Natural Science Foundation of China (Grants 30672523 and 90713037), research grants from Chinese ministry of Education (Grants 706030 and 20050316008) and program for New Century Excellent Talents in University (NCET-05-0495).

语种：英文

外文关键词：Glycogen phosphorylase; Oleanolic acid; Glucoconjugate; Inhibitor; Diabetes; Click chemistry

摘要：Synthesis and biological evaluation of glucoconjugates of oleanolic acid, linked by either a triazole moiety or an ester function, as novel inhibitors of glycogen phosphorylase have been described. Several triterpene-glycoside conjugates exhibited moderate-to-good inhibitory activity against rabbit muscle GPa. Compound 12 showed the best inhibition with an IC50 value of 1.14 mu M. Structure-activity relationship (SAR) analysis of these inhibitors is also discussed. Possible binding modes of compound 12 were explored by molecular docking simulations. (C) 2009 Elsevier Ltd. All rights reserved.