RESUMO
In a continuation of our search for potential tumor inhibitors from plants, we found that a crude extract from Ocotea leucoxylon showed selective activity typical of inhibitors of the enzyme topoisomerase I in a yeast assay for DNA-damaging agents. Using a bioassay-directed fractionation approach, the major bioactive compound was isolated and identified as the known aporphine alkaloid dicentrinone (4); the inactive alkaloid dicentrine (3) was also isolated. Compound 4 showed selective bioactivity against the rad52 repair-deficient yeast strain RS322 (IC(12) 49 microg/mL) and was inactive against the rad52- and topo1-deficient strain RS321 (IC(12) > 2000 microg/mL) and against the repair-proficient strain RJ03 (IC(12) > 2000 microg/mL). Biochemical studies with recombinant human topoisomerase I indicated that dicentrinone (4) is an inhibitor of the human enzyme. Colony formation studies suggest that it is weakly cytotoxic, but that its mechanism of toxicity differs from that of camptothecin and its derivatives.
Assuntos
Aporfinas/isolamento & purificação , Plantas Medicinais/química , Inibidores da Topoisomerase I , Aporfinas/farmacologia , Dano ao DNA/efeitos dos fármacos , DNA Super-Helicoidal/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Proteínas Recombinantes/efeitos dos fármacos , Saccharomyces cerevisiae/efeitos dos fármacos , Espectrofotometria UltravioletaRESUMO
We have identified a novel nonsteroidal ecdysteroid agonist. This compound was isolated from a methanol extract of Ajuga reptans L. (Lamiaceae) and the structure was identified by spectroscopic methods as 8-O-acetylharpagide. We have characterised this compound as an ecdysteroid agonist in a transactivation assay using beta-galactosidase as the reporter gene regulated by ecdysteroid response elements. In this assay, 8-O-acetylharpagide has an EC50 of 22 microM. The compound also competes with tritiated-ponasterone A for binding to the Drosophila ecdysteroid receptor. Finally, it induces differentiation of Drosophila Kc cells as would be expected of an ecdysteroid agonist. This iridoid glycoside is common to several plant species and may play a role in the natural defense mechanisms of plants.
Assuntos
Ecdisterona/agonistas , Plantas/metabolismo , Piranos/metabolismo , Animais , Drosophila/metabolismo , Ecdisterona/metabolismo , Hormônios de Inseto , Estrutura Molecular , Extratos Vegetais , Piranos/química , Receptores de Esteroides/metabolismoRESUMO
Curcuma comosa is a member of the economically important plant family, Zingiberaceae. A methanolic extract of C. comosa was shown to be nematocidal when tested against the free-living nematode Caenorhabditis elegans. Five diphenylheptanoids [1-5], one new and four known, have been isolated and shown to be responsible for the activity. This is the first report of three of these compounds [1, 2, 4] being isolated from a natural source.