CarbORev-5901: The First Carborane-Based Inhibitor of the 5-Lipoxygenase Pathway.
ChemMedChem
; 12(13): 1081-1086, 2017 07 06.
Article
em En
| MEDLINE
| ID: mdl-28569429
ABSTRACT
The progression of cancer is accelerated by increased proliferation, angiogenesis, and inflammation. These processes are mediated by leukotrienes. Several cancer cell lines overexpress 5-lipoxygenase, an enzyme that converts arachidonic acid into leukotrienes. An early inhibitor of the 5-lipoxygenase pathway is Rev-5901, which, however, lacks in inâ
vivo efficacy, as it is rapidly metabolized. We investigated the introduction of carboranes as highly hydrophobic and metabolically stable pharmacophores into lipoxygenase inhibitors. Carboranes are icosahedral boron clusters that are remarkably stable and used to increase the metabolic stability of unstable pharmaceutics without changing their biological activity. By introduction of meta-carborane into Rev-5901, the first carborane-based inhibitor of the 5-lipoxygenase pathway was obtained. We report the synthesis and inhibitory and cytotoxic behavior of these compounds toward several melanoma and colon cancer cell lines and their related anticancer mechanisms.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Quinolinas
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Araquidonato 5-Lipoxigenase
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Compostos de Boro
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Inibidores de Lipoxigenase
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Antineoplásicos
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Ano de publicação:
2017
Tipo de documento:
Article