Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
Bioorg Med Chem ; 11(23): 4871-9, 2003 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-14604648

RESUMO

In the course of structure-activity relationship studies, new rebeccamycin derivatives substituted in 3,9-positions on the indolocarbazole framework, and a 2',3'-anhydro derivative were prepared by semi-synthesis from rebeccamycin. The antiproliferative activities against nine tumor cell lines were determined and the effect on the cell cycle of murine leukemia L1210 cells was examined. Their DNA binding properties and inhibitory properties toward topoisomerase I and three kinases PKCzeta, CDK1/cyclin B, CDK5/p25 and a phosphatase cdc25A were evaluated. The 3,9-dihydroxy derivative is the most efficient compound of this series toward CDK1/cyclin B and CDK5/p25. It is also characterized as a DNA binding topoisomerase I poison. Its broad spectrum of molecular activities likely accounts for its cytotoxic potential. This compound which displays a tumor cell line-selectivity may represent a new lead for subsequent drug design in this series of glycosylated indolocarbazoles.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Carbazóis/síntese química , Carbazóis/farmacologia , Divisão Celular/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Indóis/síntese química , Indóis/farmacologia , Fosfotransferases/antagonistas & inibidores , Inibidores da Topoisomerase I , Animais , Antineoplásicos/química , Carbazóis/química , Linhagem Celular Tumoral , Inibidores Enzimáticos/química , Humanos , Indóis/química , Análise Espectral , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA