RESUMO
On our joint bioprospecting research on Indonesian marine invertebrates, we found moderate cytotoxicity on an extract of the sponge Dysidea sp. collected at Biak, West Papua. Separation of the extract provided two new compounds, biaketide (1) and debromoantazirine (2), along with four known molecules 3-6. The new structures were elucidated by spectroscopic analyses and by comparison with those reported. Compounds 1 and 2 showed moderate cytotoxicity against NBT-T2 cells with IC50 values of 8.3 and 4.7 µg ml(- 1), respectively.
Assuntos
Antineoplásicos/isolamento & purificação , Azirinas/isolamento & purificação , Dysidea/química , Furanos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Azirinas/química , Azirinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Furanos/química , Furanos/farmacologia , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , RatosRESUMO
Three new omega-halogenated long-chain 2H-azirines were isolated from the sponge Dysidea fragilis. Their structures revealed heterogeneity in both the composition of the terminal 1,1-dihalo-vinyl group and enantiomeric ratios at C2 of the azirine-2-carboxylate ester terminus. Azirine-2-carboxylate esters were shown to racemize spontaneously. A hypothesis is proposed for the biosynthesis of the azirinecarboxylate family of natural products that involves enzyme-catalyzed free radical halogenation followed by elimination of hydrohalic acid.
Assuntos
Azirinas/química , Fatores Biológicos/química , Dysidea/química , Animais , Apoptose/efeitos dos fármacos , Azirinas/isolamento & purificação , Azirinas/farmacologia , Fatores Biológicos/isolamento & purificação , Fatores Biológicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Halogenação , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , EstereoisomerismoRESUMO
Interleukin 1 is the prototype of an inflammatory cytokine, and evidence suggests that it uses the sphingomyelin pathway and ceramide production to trigger mitogen-activated protein kinase (MAPK) activation and subsequent gene expression required for acute inflammatory processes. To identify downstream signaling targets of ceramide, a radioiodinated photoaffinity labeling analog of ceramide ([125I] 3-trifluoromethyl-3-(m-iodophenyl)diazirine-ceramide) was employed. It is observed that ceramide specifically binds to and activates protein kinase c-Raf, leading to a subsequent activation of the MAPK cascade. Ceramide does not bind to any other member of the MAPK module nor does it bind to protein kinase C-zeta. These data identify protein kinase c-Raf as a specific molecular target for interleukin 1 beta-stimulated ceramide formation and demonstrate that ceramide is a lipid cofactor participating in regulation of c-Raf activity.