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- Title
Histone-deacetylase-targeted fluorescent ruthenium(II) polypyridyl complexes as potent anticancer agents.
- Authors
Ye, Rui-Rong; Ke, Zhuo-Feng; Tan, Cai-Ping; He, Liang; Ji, Liang-Nian; Mao, Zong-Wan
- Abstract
Histone deacetylases inhibitors (HDACis) have gained much attention as a new class of anticancer agents in recent years. Herein, we report a series of fluorescent ruthenium(II) complexes containing N(1)-hydroxy-N(8)-(1,10-phenanthrolin-5-yl)octanediamide (L), a suberoylanilide hydroxamic acid (SAHA) derivative, as a ligand. As expected, these complexes show interesting chemiphysical properties, including relatively high quantum yields, large Stokes shifts, and long emission lifetimes. The in vitro inhibitory effect of the most effective drug, [Ru(DIP)2L](PF6)2 (3; DIP: 4,7-diphenyl-1,10-phenanthroline), on histone deacetylases (HDACs) is approximately equivalent in activity to that of SAHA, and treatment with complex 3 results in increased levels of the acetylated histone H3. Complex 3 is highly active against a panel of human cancer cell lines, whereas it shows relatively much lower toxicity to normal cells. Further mechanism studies show that complex 3 can elicit cell cycle arrest and induce apoptosis through mitochondria-related pathways and the production of reactive oxygen species. These data suggest that these fluorescent ruthenium(II)-HDACi conjugates may represent a promising class of anticancer agents for potential dual imaging and therapeutic applications targeting HDACs.
- Publication
Chemistry (Weinheim an der Bergstrasse, Germany), 2013, Vol 19, Issue 31, p10160
- ISSN
1521-3765
- Publication type
Journal Article
- DOI
10.1002/chem.201300814