A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/ß-catenin pathway inhibitors in non-small-cell lung cancer cell lines.
Bioorg Med Chem
; 19(18): 5639-47, 2011 Sep 15.
Article
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| MEDLINE
| ID: mdl-21855350
ABSTRACT
We developed Wnt/ß-catenin inhibitors by identifying 13 number of 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives that were able to inhibit the Wnt/ß-catenin signal pathway and cancer cell proliferation. In the optimization process, a series of 2,3,6-trisubstituted pyrido[2,3,-b]pyrazine core skeletons showed were shown to higher activity than 2,3,6-trisubstituted quinoxaline's and thus hold promise for use as potential small-molecule inhibitors of the Wnt/ß-catenin signal pathway in non-small-cell lung cancer cell (NSCLC) lines. And we have studied the pharmacophore mapping for compound 954, which presented the highest activity with a fit value of 2.81. The pharmacophore mapping for the compounds including 954, pyrido[2,3,-b]pyrazine core had hydrogen-bond acceptor site and hydrophobic center roles.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pirazinas
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Carcinoma de Pulmón de Células no Pequeñas
/
Proteínas Wnt
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Beta Catenina
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Neoplasias Pulmonares
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Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2011
Tipo del documento:
Article