文献类型：期刊文献

英文题名：Microwave-assisted construction of triazole-linked amino acid-glucoside conjugates as novel PTP1B inhibitors

作者：He, Xiao-Peng[2,3,4,5];Li, Cui[5];Jin, Xiao-Ping[3,4];Song, Zhuo[3,4];Zhang, Hai-Lin[3,4];Zhu, Cheng-Jiang[2,3,4];Shen, Qiang[1];Zhang, Wei[1];Sheng, Li[1];Shi, Xiao-Xin[5];Tang, Yun[5];Li, Jia[1];Chen, Guo-Rong[3,4];Xie, Juan[2]

机构：[1]Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, State Key Lab Drug Res, Shanghai 201203, Peoples R China;[2]CNRS, ENS Cachan, UMR 8531, PPSM,Inst dAlembert, F-94235 Cachan, France;[3]E China Univ Sci & Technol, Key Lab Adv Mat, Shanghai 200237, Peoples R China;[4]E China Univ Sci & Technol, Inst Fine Chem, Shanghai 200237, Peoples R China;[5]E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2011

卷号：35

期号：3

起止页码：622

外文期刊名：NEW JOURNAL OF CHEMISTRY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000287867300016)】；

基金：X.-P. He gratefully acknowledges the French Embassy in Beijing, China, for a doctorate fellowship. C.-J. Zhu thanks the French Ministry of Foreign Affairs for an Eiffel Doctorate fellowship. This project is supported by CNRS and ENS Cachan. Grants were also from the National Natural Science Foundation of China (Grant No. 20876045 and 30801405), National Basic Research Program of China (No. 2007CB914201), National Science & Technology Major Project of China "Key New Drug Creation and Manufacturing Program'' (No. 2009ZX09302-001), Shanghai Science and Technology Community (No. 10410702700 and 09DZ2291200), and the Chinese Academy of Sciences (No. KSCX2-YW-R-168).

语种：英文

摘要：There has been increasing interest in the development of protein tyrosine phosphatase 1B (PTP1B) inhibitors for the treatment of type 2 diabetes, obesity and breast cancer. We report here the identification of a series of mono-and bis-phenylalaninyl and tyrosinyl glucoside derivatives as novel PTP1B inhibitors. The designed compounds bearing one or two phenylalanine or tyrosine derivatives on the 6-, 2,3-, 2,6-, 3,4- and 4,6-positions of the glucosyl scaffolds were efficiently constructed via the microwave-assisted Cu(I)-catalyzed azide-alkyne cycloaddition in moderate-to-excellent yields. Successive biological assays identified these compounds as novel PTP1B inhibitors, with the 4,6-disubstituted tyrosinyl glucoside being the most potent. A kinetic study established that both mono-and bis-triazole-linked glycosyl acids act as typical competitive inhibitors whereas the bis-triazolyl ester that also exhibited inhibitory activity on PTP1B displayed a mixed-type inhibition pattern. Furthermore, docking simulation plausibly proposed the diverse binding modes of these compounds with the enzymatic target.