RESUMO
Cytotoxicity-guided fractionation of an organic solvent extract of the plant Crossosoma bigelovii led to the discovery of a new strophanthidin glycoside (1) and two new 2-methylchromone glycosides (2 and 3). Also isolated were the known chromones eugenin and noreugenin, the indole alkaloid ajmalicine, the dibenzylbutane lignan secoisolariciresinol, the dibenzylbutyrolactone lignan matairesinol, and the furanone 5-tetradec-5-enyldihydrofuran-2-one. Further investigation into the biological properties of strophanthidin glycosides revealed a connection between inhibition of HIF-1 activation and the glycosylation of the genin. This work is the first published study of the bioactive phytochemicals of the family Crossosomataceae.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Cardenolídeos/isolamento & purificação , Cardenolídeos/farmacologia , Cromonas/isolamento & purificação , Cromonas/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Magnoliopsida/química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/química , Butileno Glicóis/química , Butileno Glicóis/isolamento & purificação , Cardenolídeos/química , Cromonas/química , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Furanos/química , Furanos/isolamento & purificação , Glicosídeos/química , Células HT29 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Lignanas/química , Lignanas/isolamento & purificação , México , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Relação Estrutura-AtividadeRESUMO
Two new chondropsin-type macrolide lactams, poecillastrins B (1) and C (2), were isolated from aqueous extracts of the marine sponge Poecillastra sp. These trace metabolites were isolated in low yield (400-600 microg), and their structures were determined primarily by analysis of NMR data acquired using a cyrogenically cooled probe. High-quality 1D and 2D NMR data sets allowed complete assignment of the spectroscopic data and defined the new structures as 35-membered ring analogues of poecillastrin A (3). Compounds 1 and 2 showed potent cytotoxic activity against a human melanoma tumor cell line (LOX) with an IC50 value of less than 1 microg/mL.