文献类型：期刊文献

英文题名：Monosaccharide as a central scaffold toward the construction of salicylate-based bidentate PTP1B inhibitors via click chemistry

作者：Tang, Yan-Hui[1]; Hu, Min[1]; He, Xiao-Peng[1]; Fahnbulleh, Sando[1]; Li, Cui[1]; Gao, Li-Xin[2]; Sheng, Li[2]; Tang, Yun[1]; Li, Jia[2]; Chen, Guo-Rong[1]

机构：[1] Key Laboratory for Advanced Materials, Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, China; [2] National Center for Drug Screening, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China

年份：2011

卷号：32

期号：3

起止页码：1000

外文期刊名：Bulletin of the Korean Chemical Society

收录：EI(收录号：20111413893216)

语种：英文

外文关键词：Binding energy - Synthesis (chemical) - Glucose - Phosphatases - Scaffolds (biology)

摘要：The discovery of carbohydrate-based bioactive compounds has recently received considerable interest in the drug development. This paper stresses on the application of 1-methoxy-O-glucoside as the central scaffold, whereas salicylic pharmacophores were introduced with diverse spatial orientations probing into the structural preference of an enzymatic target, i.e. protein tyrosine phosphatase 1B (PTP1B). By employing regioselective protection and deprotection strategy, 2,6-, 3,4-, 4,6- and 2,3-di-O-propynyl 1-methoxy-O-glucosides were previously synthesized and then coupled with azido salicylate via click chemistry in forming the desired bidentate salicylic glucosides with high yields. The inhibitory assay of the obtained triazolyl derivatives leads to the identification of the 2,3-disubstituted salicylic 1-methoxy-O-glucoside as the structurally privileged PTP1B inhibitor among this bidentate compound series with micromole-ranged IC50 value and reasonable selectivity over other homologous PTPs tested. In addition, docking simulation was conducted to propose a plausible binding mode of this authorized inhibitor with PTP1B. This research might furnish new insight toward the construction of structurally different bioactive compounds based on the monosaccharide scaffold. Copyright ? 2005 KCSNET.