期刊
CHEMISTRYSELECT
卷 5, 期 23, 页码 7069-7075出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/slct.202001282
关键词
Anticancer agents; Cytotoxicity; DNA cleavage; Enediynes; Propargyl-allenyl
资金
- National Natural Science Foundation of China [21871080, 21503078, 21474027]
- Fundamental Research Funds for the Central Universities [22221818014]
- Shanghai Leading Academic Discipline Project [B502]
- Shanghai local government
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据