Benzimidazole and imidazole inhibitors of histone deacetylases: Synthesis and biological activity.
Bioorg Med Chem Lett
; 20(10): 3138-41, 2010 May 15.
Article
em En
| MEDLINE
| ID: mdl-20392637
ABSTRACT
A series of N-hydroxy-3-[3-(1-substituted-1H-benzoimidazol-2-yl)-phenyl]-acrylamides (5a-5ab) and N-hydroxy-3-[3-(1,4,5-trisubstituted-1H-imidazol-2-yl)-phenyl]-acrylamides (12a-s) were designed, synthesized, and found to be nanomolar inhibitors of human histone deacetylases. Multiple compounds bearing an N1-piperidine demonstrate EC(50)s of 20-100 nM in human A549, HL60, and PC3 cells, in vitro and in vivo hyperacetylation of histones H3 and H4, and induction of p21(waf). Compound 5x displays efficacy in human tumor xenograft models.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzimidazóis
/
Inibidores de Histona Desacetilases
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Histona Desacetilases
/
Imidazóis
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article