文献类型：期刊文献

英文题名：Preparation and antitumor applications of asymmetric propargyl amide maleimide based enediyne antibiotics

作者：Wang, Yue[1];Li, Baojun[1];Zhang, Mengsi[1];Lu, Haotian[1];Chen, Huimin[1];Wang, Wenbo[1];Ding, Yun[1];Hu, Aiguo[1]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Adv Polymer Mat, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China

年份：2020

卷号：76

期号：24

外文期刊名：TETRAHEDRON

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000537423800001)】；

基金：YW (#) and BL (#) contribute equally to this work. The financial supports from National Natural Science Foundation of China (21871080, 21503078), the Fundamental Research Funds for the Central Universities (22221818014), and Shanghai Leading Academic Discipline Project (B502) are greatly acknowledged. AH thanks the "Eastern Scholar Professorship" support from Shanghai Local Government. AH thanks Profs. Runhui Liu and Junyou Wang for their kindly advice and help in cell experiments.

语种：英文

外文关键词：Antitumor agents; Cytotoxicity; DNA cleavage; Enediyne; Rearrangement

摘要：Maleimide-based enediynes with propargyl amide at one arm and other kinds of alkyne at the other arm were synthesized via Sonogashira reaction. The logP values of these enediyne antibiotics were adjusted by changing the alkyl chain length and installing a hydroxyl group. As confirmed by electron paramagnetic resonance analysis, the enediynes generated reactive free radicals at physiological temperature, which endows them the ability to cause DNA cleavage and lead to tumor cell death. While most of the enediynes act in small molecular form, one of them showed amphiphilic property and formed vesicles in deionized water for potential self-delivery applications. The reactive oxygen species level in tumor cells was enhanced in the presence of these enediynes, leading to cell death through apoptosis pathway. The half inhibition concentrations (IC50) of the enediynes towards HeLa cells were on the micromolar level, comparable to many commercial anticancer agents. (C) 2020 Published by Elsevier Ltd.