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-Atividade