Coordination-Accelerated Radical Formation from Acyclic Enediynes for Tumor Cell Suppression.

Abstract

A maleimide-based acyclic enediyne with salicylaldiminato substituents at the alkyne termini was synthesized, which was further chelated with three kinds of metal-ions, CuII , ZnII , and MgII , and form metalloenediynes. The cycloaromatization of this thermally inactive enediyne ligand was greatly accelerated through the coordination with metal ions. Specifically, the CuII -metalloenediyne showed an extremely low onset temperature of 55 °C and underwent spontaneous cycloaromatization at ambient temperature to produce free radicals, followed by generation of reactive oxygen species in the physiological environment. The metalloenediyne exhibited excellent DNA cleavage ability and high cytotoxicity towards HeLa cells, with half-maximal inhibitory concentration values comparable to many commercial antitumor agents. The combination of the electron-withdrawing effect of the maleimide moiety at the ene position and metal coordination at the yne termini provides a new inspiration for designing and synthesizing highly efficient enediyne antitumor agents.

• Authors: Baojun Li, Mengsi Zhang, Haotian Lu, Hailong Ma, Yue Wang, Huimin Chen, Yun Ding, Aiguo Hu
• Journal: Chemistry, an Asian journal (Chem Asian J) Vol. 14 Issue 23 Pg. 4352-4357 (Dec 02 2019) ISSN: 1861-471X [Electronic] Germany
• PMID: 31777169 (Publication Type: Journal Article)
• Copyright: © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• Enediynes
• Free Radicals
• Ligands
• Maleimides
• Metals
• Reactive Oxygen Species
• maleimide

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Survival (drug effects)
• DNA Cleavage (drug effects)
• Enediynes (chemistry)
• Free Radicals (chemistry, metabolism)
• HeLa Cells
• Humans
• Ligands
• Maleimides (chemistry)
• Metals (chemistry)
• Reactive Oxygen Species (metabolism)