RESUMO
In a study to evaluate celastroloids as potential anticancer agents, demethylzeylasterone (5), a 6-oxophenolic triterpenoid from Kokoona zeylanica, was found to be an inhibitor of the enzyme topoisomerase IIalpha (IC(50) = 17.6 microM). Studies of the relationship of this inhibitor to both DNA and the enzyme resulted in 5 being classified as a "catalytic inhibitor" of topoisomerase II. Demethylzeylasterone selectively inhibits the growth of the breast cancer cell line MCF-7 (IC(50) = 12.5 microM) without inhibiting the growth of non-small cell lung cancer (NCI-H460) and CNS glioma (SF-268) cell lines. This is the first report of topoisomerase II inhibitory activity in a celastroloid.
Assuntos
Antineoplásicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Plantas Medicinais/química , Inibidores da Topoisomerase II , Triterpenos/isolamento & purificação , Antígenos de Neoplasias , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama , Carcinoma Pulmonar de Células não Pequenas , Catálise , DNA/antagonistas & inibidores , DNA Topoisomerases Tipo II , Proteínas de Ligação a DNA , Eletroforese em Gel de Ágar , Ensaio de Desvio de Mobilidade Eletroforética , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Feminino , Glioma , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares , Verde de Metila , Estrutura Molecular , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/metabolismo , Relação Estrutura-Atividade , Triterpenos/química , Triterpenos/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
An activity-guided fractionation of a methanol-dichloromethane extract obtained from the aerial parts of Eysenhardtia texana led to the isolation of two novel antibacterial and antifungal flavanones together with a known flavanone. Their structures were established as 4',5,7-trihydroxy-8-methyl-6-(3-methyl-[2-butenyl])-(2S)-flavanone, 4',5,7-trihydroxy-6-methyl-8-(3-methyl-[2-butenyl])-(2S)-flavanone and 4',5-dihydroxy-7-methoxy-6-(3-methyl-[2-butenyl])-(2S)-flavanone on the basis of their UV, 1D and 2D-NMR spectra.