Design, synthesis and preliminary evaluation of a series of histone deacetylase inhibitors carrying a benzodiazepine ring.
Eur J Med Chem
; 66: 56-68, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23792316
ABSTRACT
A series of new histone deacetylase inhibitors were designed and synthesized based on hybridization between SAHA or oxamflatin and 5-phenyl-1,4-benzodiazepines. The compounds were tested for their enzyme inhibitory activity on HeLa nuclear extracts, and on human recombinant HDAC1 and HDAC6. Antiproliferative activity was tested on different cancer cells types, while proapoptotic activity was primarily tested on NB4 cells. The compounds showed IC50 values similar to those of SAHA. Compound (S)-8 displayed interesting activity against hematological and solid malignancies.
Palavras-chave
1,4-Benzodiazepine; 5-phenyl-1,4-benzodiazepine; AML; Antiproliferative activity; Apoptosis; BDZ; BOP-Cl; ER; Enantioselectivity; FXRQXSOJXFXFKW-UHFFFAOYSA-N; GQKBLEVLBFZGSR-UHFFFAOYSA-N; HDAC; HDAC inhibitors; HRABXMKDRVKZIZ-UXBLZVDNSA-N; NHGNWJXVKSKUTQ-UHFFFAOYSA-N; PGWVWMQPVNCSBB-UHFFFAOYSA-N; PKFJHSNYEZYYGI-UHFFFAOYSA-N; QNDUGSJDIKUKHC-UHFFFAOYSA-N; SAHA; SZERHQGPLCARMH-UHFFFAOYSA-N; XPOXSSWYTUEULK-UHFFFAOYSA-N; ZEZRNDUSXIQAAE-HNNXBMFYSA-N; acute myeloid leukemia; bis(2-oxo-3-oxazolidinyl)phosphonic chloride; eudismic ratio; histone deacetylase; suberoylanilide hydroxamic acid
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Benzodiazepinas
/
Desenho de Fármacos
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Inibidores de Histona Desacetilases
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Histona Desacetilases
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article