Antiproliferative diarylpyrazole derivatives as dual inhibitors of the ERK pathway and COX-2.
Chem Biol Drug Des
; 82(3): 336-47, 2013 Sep.
Article
em En
| MEDLINE
| ID: mdl-23834707
ABSTRACT
A series of 3,4-diarylpyrazole-1-carboxamide derivatives was designed and synthesized. A selected group of the target compounds was tested for in vitro antiproliferative activities over a panel of 60 cancer cell lines at the National Cancer Institute (NCI, Bethesda, MD, USA) at a single-dose concentration of 10 µm, and the four most active compounds 9a, 9l, 9n, and 10o were further tested in a five-dose testing mode to determine their IC50 values over the 60 cell lines. In addition, a selected group of target compounds were tested for inhibitory effect over cyclooxygenase isozymes. Compounds 9a, 9l, 9n, and 10o were also tested for MEK and ERK kinase inhibitory activity using Western blot assay. Compound 10o was selective toward melanoma cell line subpanel, and its antiproliferative activity may be attributed to selective cyclooxygenase-2 inhibition and ERK pathway inhibition.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperazinas
/
Pirazóis
/
MAP Quinase Quinase Quinases
/
MAP Quinases Reguladas por Sinal Extracelular
/
Inibidores de Proteínas Quinases
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Ciclo-Oxigenase 2
/
Inibidores de Ciclo-Oxigenase 2
Limite:
Humans
Idioma:
En
Revista:
Chem Biol Drug Des
Assunto da revista:
BIOQUIMICA
/
FARMACIA
/
FARMACOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Egito