RESUMO
Fractionation of the extract of the marine cyanobacterium Lyngbya majuscula collected from Panama led to the isolation of malyngolide dimer (1). The planar structure of 1 was determined using 1D and 2D NMR spectroscopy and HRESI-TOFMS. The absolute configuration was established by chemical degradation followed by chiral GC-MS analyses and comparisons with an authentic sample of malyngolide seco-acid (4). Compound 1 showed moderate in vitro antimalarial activity against chloroquine-resistant Plasmodium falciparum (W2) (IC(50) = 19 microM) but roughly equivalent toxicity against H-460 human lung cell lines. Furthermore, because the closely related cyanobacterial natural product tanikolide dimer (5) was a potent SIRT2 inhibitor, compound 1 was evaluated in this assay but found to be essentially inactive.
Assuntos
Cianobactérias/química , Éteres Cíclicos/isolamento & purificação , Éteres Cíclicos/farmacologia , Toxinas de Lyngbya/química , Toxinas de Lyngbya/isolamento & purificação , Plasmodium falciparum/efeitos dos fármacos , Cloroquina/farmacologia , Resistência a Medicamentos/efeitos dos fármacos , Éteres Cíclicos/química , Humanos , Lactonas/química , Lactonas/isolamento & purificação , Toxinas de Lyngbya/farmacologia , Biologia Marinha , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Panamá , Testes de Sensibilidade Parasitária , Pironas/química , Pironas/isolamento & purificação , Pironas/farmacologia , Relação Estrutura-AtividadeRESUMO
A chloroform extract of cultured Prorocentrum lima was analyzed for carboxylic polyethers related to okadaic acid (OA). The extract was derivatized with 1-(bromoacetyl)pyrene to give the fluorescent pyrenacyl esters of OA and other carboxylic acids. The resulting mixture was subjected to preparative high performance liquid chromatography with fluorescence detection. Positive chemical ionization mass spectrometry indicated that four OA-related compounds were present, including two methylated analogues. The fragmentation pattern of at least one of these suggests it is not the previously reported 35-methylokadaic acid.