Histone‐Deacetylase‐Targeted Fluorescent Ruthenium(II) Polypyridyl Complexes as Potent Anticancer Agents
- 4 July 2013
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 19 (31), 10160-10169
- https://doi.org/10.1002/chem.201300814
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 N1‐hydroxy‐N8‐(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.Keywords
Funding Information
- State High-Tech Development Program (2012AA020305)
- National Natural Science Foundation of China (21172274, 21201183, 21203256, 21231007)
- Guangdong Provincial Natural Science Foundation (9351027501000003)
- Chinese Ministry of Education (313058)
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