文献类型：期刊文献

英文题名：Preparation of Maleimide-Based Enediynes with Propargyl Ester for Efficient Tumor Cell Suppression

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

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

年份：2020

卷号：5

期号：23

起止页码：7069

外文期刊名：CHEMISTRYSELECT

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000542282800029)】；

基金：The authors gratefully acknowledge the financial support from National Natural Science Foundation of China (21871080, 21503078, 21474027), the Fundamental Research Funds for the Central Universities (22221818014), and Shanghai Leading Academic Discipline Project (B502). AH thanks the "Eastern Scholar Professorship" support from Shanghai local government. We thank Profs. Runhui Liu and Junyou Wang for his kind advice in cellular experiments.

语种：英文

外文关键词：Anticancer agents; Cytotoxicity; DNA cleavage; Enediynes; Propargyl-allenyl

摘要：Acyclic enediynes are much easier to be synthesized comparing to natural or synthetic cyclic enediynes. However, the conditions for their thermal reactions to produce free radicals through Bergman cyclization (BC) are typically demanding, limiting their applications as antitumor agents. On the other hand, the acyclic compounds with enyne-allene structures prone to proceed through Myers-Saito cyclization (MCS) under much milder conditions. Therefore, it is vital to design acyclic enediynes which can permit propargyl-allenyl rearrangement and then undergo MSC at low temperature for antitumor applications. In this work, we synthesized a series of maleimide-based enediyne compounds with propargyl ester functionalities. The facile propargyl-allenyl tautomerization assisted by the maleimide group enabled the formation of enyne-allene structures and the subsequent occurrence of MSC. The generation of free radicals, which further raised the reactive oxygen species level in physiological environments, was confirmed by electron paramagnetic resonance analysis. The highly reactive radicals showed excellent DNA-cleaving ability as confirmed with DNA gel electrophoresis. In addition, this kind of acyclic enediynes effectively inhibited the proliferation of HeLa cells with half inhibition concentration down to submicromolar level, comparable or even superior to many clinically used antitumor agents, showing promising application aspect.