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Bioorg Med Chem Lett ; 21(19): 5735-8, 2011 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-21875796

RESUMEN

The enzymatic inhibition of histone deacetylase activity has come out as a novel and effectual means for the treatment of cancer. Two novel series of 2-[5-(4-substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino]-pyrimidine-5-carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized as novel hydroxamic acid based histone deacetylase inhibitors. The antiproliferative activities of the compounds were investigated in vitro using histone deacetylase inhibitory assay and MTT assay. The synthesized compounds were also tested for antitumor activity against Ehrlich ascites carcinoma cells in Swiss albino mice. The efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid based histone deacetylase inhibitor.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/síntesis química , Diseño de Fármacos , Inhibidores de Histona Desacetilasas/química , Inhibidores de Histona Desacetilasas/síntesis química , Oxadiazoles/química , Tiadiazoles/química , Animales , Antineoplásicos/farmacología , Carcinoma de Ehrlich/tratamiento farmacológico , Proliferación Celular , Evaluación Preclínica de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/química , Ratones , Neoplasias/tratamiento farmacológico , Relación Estructura-Actividad , Propiedades de Superficie , Zinc/química
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