853649-55-5Relevant articles and documents
An acyclic enediyne anticancer compound attributed to a Bergman cyclization at physiological temperature
Li, Baojun,Duan, Bing,Li, Jing,Zhang, Mengsi,Yuan, Yuan,Ding, Yun,Hu, Aiguo
, p. 6419 - 6425 (2018)
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.
Self-Delivery Nanoparticles of Amphiphilic Acyclic Enediynes for Efficient Tumor Cell Suppression
Li, Jing,Wu, Yuequn,Sun, Lili,Huang, Shuai,Li, Baojun,Ding, Yun,Hu, Aiguo
supporting information, p. 479 - 485 (2019/03/29)
Four acyclic maleimide-based enediyne compounds with different hydrophilicity were synthesized through Sonogashira reaction to reveal a self-delivery antitumor drug platform. As proved by ESR analysis, the enediyne compounds undergo Bergman-like cyclization and generate diradical intermediates at physiological temperature, which are able to induce DNA-cleavage through the abstraction of H atoms from the sugar-phosphate backbones. When the critical aggregation concentration is reached in water, the amphiphilic enediyne compounds self-assemble into nanoparticles and possess the self-delivery ability to be facilely admitted by tumor cells, resulting in greatly improved cytotoxicity (IC50 down to 10 μmol·L–1) and much higher tumor cell apoptosis rate (up to 86.6%) in comparison with either the hydrophilic or the lipophilic enediyne compound. The enhanced endocytosis of the amphiphilic enediyne compounds was further confirmed through confocal laser scanning microscopy analysis. The unveiled relationship between the hydrophilicity of enediyne drugs and their therapeutic efficacy will provide a guideline for the design of new self-delivery drugs employed in medicinal applications.
Maleimide-based acyclic enediyne for efficient DNA-cleavage and tumor cell suppression
Song, Depeng,Sun, Shiyuan,Tian, Yu,Huang, Shuai,Ding, Yun,Yuan, Yuan,Hu, Aiguo
supporting information, p. 3195 - 3200 (2015/04/27)
A pH-sensitive acyclic enediyne (1) was synthesized for efficient DNA-cleavage and tumor cell suppression. Unlike other acyclic enediynes, this novel enediyne transforms into a highly reactive enediyne (2) in an acidic environment only, which undergoes Be
