文献类型：期刊文献

英文题名：Synthesis of a glucose conjugate of pristimerin and evaluation of its anticancer activity

作者：Yang, Fan[1,2];Zhang, Jie[1];Li, Jiacheng[2];Ye, Wenbo[2,3];Li, Ang[2];He, Weiwei[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, Ctr Excellence Mol Synth, Shanghai 200032, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Innovat Res Inst Tradit Chinese Med, Res Ctr Chiral Drugs, Shanghai 201203, Peoples R China

年份：2023

卷号：34

期号：1

外文期刊名：CHINESE CHEMICAL LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000893634100017)】；

基金：This paper is dedicated to Prof. Guo-Qiang Lin. This work was supported by Ministry of Science and Technology (Na-tional Key Research and Development Program of China, No. 2018YFA0901900) , National Natural Science Foundation of China (Nos. 21931014, U2002221, 21772225, 21572064, 81502956 and 21621002) , Chinese Academy of Sciences (Strategic Priority Re-search Program, No. XDB20000000; International Partner Program, No. 121731KYSB20190039; Key Research Program of Frontier Sci-ences, No. QYZDB-SSW-SLH040) , Science and Technology Commis-sion of Shanghai Municipality (Nos. 20430713400, 17XD140460 0 and JCYJ-SHFY-2022-0 05) .

语种：英文

外文关键词：Glucose conjugation; Warburg effect; Pristimerin; Extracellular stability

摘要：Taking advantage of the Warburg effect in cancer cells, glucose conjugation has emerged as a useful strategy for targeted delivery of anticancer agents. Pristimerin is a naturally occurring triterpenoid that displays potent but non-selective cytotoxicity. We developed a convergent and modular approach to con-struction of glucose -payload conjugates featuring copper-mediated azide -alkyne cycloaddition and pre-pared a glucose conjugate of pristimerin through this approach. The anticancer activity of this conjugate was evaluated in cancer cells and normal cells; however, the selectivity toward cancer cells was not sig-nificantly improved. We then examined the extracellular stability of the conjugate and found that its ester linkage was cleaved rapidly in Dulbecco's Modified Eagle's Medium at 37 degrees C, which resulted in the release of pristimerin. In fact, the inorganic components in this medium were sufficient to induce the cleavage. Given that the subtle difference between intrinsic stability and extracellular stability of the conjugate linker is often underappreciated, this work highlights the importance of the latter in the development of target-selective conjugates.(c) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.