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J Med Chem ; 58(2): 692-704, 2015 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-25496412

RESUMEN

A series of conformationally flexible furan-derived allocolchicinoids was prepared from commercially available colchicine in good to excellent yields using a three-step reaction sequence. Cytotoxicity studies indicated the potent activity of two compounds against human epithelial and lymphoid cell lines (AsPC-1, HEK293, and Jurkat) as well as against Wnt-1 related murine epithelial cell line W1308. The results of in vitro experiments demonstrated that the major effect of these compounds was the induction of cell cycle arrest in the G2/M phase as a direct consequence of effective tubulin binding. In vivo testing of the most potent furanoallocolchicinoid 10c using C57BL/6 mice inoculated with Wnt-1 tumor cells indicated significant inhibition of the tumor growth.


Asunto(s)
Antineoplásicos/síntesis química , Colchicina/análogos & derivados , Furanos/síntesis química , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Colchicina/farmacología , Furanos/farmacología , Humanos , Ratones , Ratones Endogámicos C57BL , Microtúbulos/efectos de los fármacos , Modelos Moleculares , Relación Estructura-Actividad , Moduladores de Tubulina/síntesis química
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