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Bioorg Med Chem ; 18(7): 2474-84, 2010 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-20303770

RESUMO

Certain steroidal compounds have demonstrated an antiproliferative effect against several tumor cell lines; however, their complete role on cancer cells is not currently established. Herein, we report the synthesis and evaluation of two new 26-hydroxy-22-oxocholestanic steroids on cervical cancer CaSki cells. The title compounds were prepared from diosgenin and hecogenin in excellent yields. We determined their effect on cell proliferation, cell cycle, and cell death. The cytotoxic effect of the title compounds on CaSki and human lymphocytes was also evaluated, indicating that the main cell death process is not necrosis; the null effect on lymphocytes implies that they are not cytotoxic. The observation of apoptotic bodies as well as the increase in the expression of active caspase-3 along with the fragmentation of DNA confirmed that such new cholestanic frameworks induced apoptosis in tumor cells. Significantly, their antiproliferative activity on tumor cells did not affect the proliferative potential of normal fibroblasts from cervix and peripheral blood lymphocytes. The title compounds show selective antitumor activity and therefore serve as promising lead candidates for further optimization.


Assuntos
Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Colestanóis/química , Colestanóis/síntese química , Colestanóis/farmacologia , Diosgenina/química , Sapogeninas/química , Esteroides/química , Esteroides/síntese química , Esteroides/farmacologia , Sequência de Carboidratos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Corantes Fluorescentes , Humanos , Marcação In Situ das Extremidades Cortadas , Indóis , Linfócitos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Dados de Sequência Molecular , Relação Estrutura-Atividade , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/patologia
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