文献类型：期刊文献

英文题名：An acyclic enediyne anticancer compound attributed to a Bergman cyclization at physiological temperature

作者：Li, Baojun[1];Duan, Bing[2];Li, Jing[1];Zhang, Mengsi[1];Yuan, Yuan;Ding, Yun[1,2];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;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

年份：2018

卷号：74

期号：44

起止页码：6419

外文期刊名：TETRAHEDRON

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000447576800005)】；

基金：Dedicated to Prof, Ji-tao Wang on the occasion of his 100th birthday. The authors gratefully acknowledge the financial support from National Natural Science Foundation of China (21474027, 21503078, 21871080), 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.

语种：英文

外文关键词：Anticancer agents; Bergman cyclization; Cytotoxicity; DNA cleavage; Enediyne

摘要：Enediyne cytotoxic drugs have attracted much attention because of their unique structure and potent anticancer activity. However, acyclic enediynes are long considered as inactive at physiological temperature due to their long C1-C6 distance. By adjusting the steric bulkiness of the functional groups at the alkynyl termini and the electron-withdrawing effect at the ene moiety, herein, a simple acyclic enediyne was designed and synthesized to achieve the onset of thermal Bergman cyclization at physiological temperature in polar solvents. The spontaneous generation of diradical intermediates was confirmed through EPR analysis and further supported by spin trapping experiment, radical indicator experiment, and high resolution MS analysis. The reactive diradicals generated in aqueous media induced single and double stranded cleavage of DNA, and showed high cytotoxicity to Hela cells, The IC50 value of the enediyne compound is comparable to many clinical used anti-tumor agents. (C) 2018 Elsevier Ltd. All rights reserved.