Design, synthesis and biological evaluation of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy.
Eur J Med Chem
; 157: 909-924, 2018 Sep 05.
Article
em En
| MEDLINE
| ID: mdl-30149323
ABSTRACT
A series of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy were designed, synthesized and biologically evaluated. Among them, compound 7l displayed the most potent inhibitory against COX-2 (IC50â¯=â¯0.82⯵M) and antiproliferative activities against Hela cells (IC50â¯=â¯0.34⯵M) compared with Celecoxib (IC50â¯=â¯0.38 and 7.91⯵M). The further mechanistic studies revealed that 7l could induce apoptosis of Hela cells by mitochondrial depolarization and the antiproliferative activities of 7l were positively correlated with the levels of intracellular NO release in Hela cells. Most notably, 7l could dramatically suppress tumor growth in Hela cells xenografted mouse model. In summary, compound 7l may be promising candidates for cancer therapy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
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Compostos Ferrosos
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Desenho de Fármacos
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Doadores de Óxido Nítrico
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Ciclo-Oxigenase 2
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Inibidores de Ciclo-Oxigenase 2
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Metalocenos
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Neoplasias Experimentais
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Antineoplásicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2018
Tipo de documento:
Article