Premium
Histone‐Deacetylase‐Targeted Fluorescent Ruthenium(II) Polypyridyl Complexes as Potent Anticancer Agents
Author(s) -
Ye RuiRong,
Ke ZhuoFeng,
Tan CaiPing,
He Liang,
Ji LiangNian,
Mao ZongWan
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201300814
Subject(s) - ruthenium , histone deacetylase , chemistry , acetylation , histone , apoptosis , histone h3 , histone deacetylase inhibitor , hydroxamic acid , ligand (biochemistry) , reactive oxygen species , cancer research , biochemistry , stereochemistry , biology , receptor , dna , gene , catalysis
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) 2 L ](PF 6 ) 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.