An acyclic enediyne anticancer compound attributed to a Bergman cyclization at physiological temperature |
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Authors: | Baojun Li Bing Duan Jing Li Mengsi Zhang Yuan Yuan Yun Ding Aiguo Hu |
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Affiliation: | 1. Shanghai Key Laboratory of Advanced Polymeric Materials, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, China;2. The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China |
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Abstract: | 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. |
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Keywords: | Anticancer agents Bergman cyclization Cytotoxicity DNA cleavage Enediyne |
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