Maleimide-based acyclic enediyne for efficient DNA-cleavage and tumor cell suppression.

Abstract

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 Bergman cyclization spontaneously at ambient temperature. An EPR study on the enediyne 2 confirmed the generation of free radicals through Bergman cyclization. The activated enediyne induced DNA-cleavage and exhibited cytotoxicity towards various tumor cells under the action of diradicals arising from spontaneous Bergman cyclization at physiological temperature. These findings suggest a novel strategy of anticancer drug design, where the activation of the silent compound takes place under the acidic environment inside the tumor cells.

• Authors: Depeng Song , Shiyuan Sun , Yu Tian , Shuai Huang , Yun Ding , Yuan Yuan , Aiguo Hu
• Journal: Journal of materials chemistry. B (J Mater Chem B) Vol. 3 Issue 16 Pg. 3195-3200 (Apr 28 2015) ISSN: 2050-7518 [Electronic] England
• PMID: 32262313 (Publication Type: Journal Article)