RESUMO
In the course of studies on the preparation of potential kinase inhibitors, we were interested in the synthesis of diversely substituted glycosyl-isoindigo derivatives. To get an insight into the effect of the substitution pattern of the isoindigo aromatic and carbohydrate moieties on the biological activities and to identify the cellular target(s) involved in the in-vitro antiproliferative activity of these derivatives, their inhibitory activities toward a panel of 10 different kinases were examined. The best inhibitory activities were found toward cyclin-dependent kinase 2/cyclin A. Molecular modelling experiments were carried out to investigate the binding interactions between the active site of cyclin-dependent kinase 2 and the lead compound of this series.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Indóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Glicosilação , Humanos , Indóis/química , Modelos Moleculares , Estrutura Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/química , Proteínas Quinases/química , Relação Estrutura-AtividadeRESUMO
A convenient synthesis of indolin-2-ones substituted in the 3 position by an aminomethylene group bearing different amino acid moieties is described. Their antiproliferative activities were evaluated toward a panel of human solid tumor cell lines (PC 3, DLD-1, MCF-7, M4 Beu, A549, PA 1) and healthy cell lines (a murine fibroblast L929 and a human fibroblast primary culture).
Assuntos
Aminoácidos/química , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Indóis/síntese química , Indóis/farmacologia , Antineoplásicos/química , Indóis/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Espectrofotometria InfravermelhoRESUMO
In the course of structure-activity relationship studies, diversely substituted 1-(beta-D-glucopyranosyl)-isoindigo derivatives were prepared from commercially available indolines. Their antiproliferative activities were evaluated toward a panel of human solid cancer cell lines (PC 3, DLD-1, MCF-7, M4Beu, A549, PA 1), a murine cell line (L929) and a human fibroblast primary culture to get an insight into the substitution pattern required for the best biological potencies.
