Phenylpyrrole-based HDAC inhibitors: synthesis, molecular modeling and biological studies.
Future Med Chem
; 8(13): 1573-87, 2016 09.
Article
em En
| MEDLINE
| ID: mdl-27556815
ABSTRACT
AIM:
Histone deacetylases (HDACs) regulate the expression and activity of numerous proteins involved in the initiation and progression of cancer. Currently, three hydroxamate-containing HDAC pan-inhibitors have been approved as antitumor agents.RESULTS:
We herein present the development of a series of novel phenylpyrrole-based derivatives stemmed from combined computational and medicinal chemistry efforts to rationally modulate HDAC1/6 isoform selectivity. In vitro activity on HDAC1 and HDAC6 isoforms and the effects of selected analogs on histone H3 and α-tubulin acetylation levels were determined. Cell-based data evidenced, for selected compounds, a promising antitumor potential and low toxicity on normal cells.CONCLUSION:
The newly developed compounds represent a valuable starting point for the development of novel anticancer agents.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirróis
/
Histona Desacetilase 1
/
Inibidores de Histona Desacetilases
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Histona Desacetilases
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article