RESUMO
Abstract: Cembrane-type diterpenoids are among the most frequently encountered natural products from the soft corals of the genus Lobophytum. In the course of our investigation to identify anti-inflammatory constituents from a wild-type soft coral Lobophytumcrassum, two new cembranoids, lobophyolide A (1) and B (2), along with five known compounds (3-7), were isolated. The structures of these natural products were identified using NMR and MS spectroscopic analyses. Compound 1 was found to possess the first identified α-epoxylactone group among all cembrane-type diterpenoids. The in vitro anti-inflammatory effect of compounds 1-5 was evaluated. The results showed that compounds 1-5 not only reduced IL-12 release, but also attenuated NO production in LPS-activated dendritic cells. Our data indicated that the isolated series of cembrane-type diterpenoids demonstrated interesting structural features and anti-inflammatory activity which could be further developed into therapeutic entities.
Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Células Dendríticas/efeitos dos fármacos , Diterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Diterpenos/química , Diterpenos/isolamento & purificação , Interleucina-12/metabolismo , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Óxido Nítrico/metabolismo , Cultura Primária de Células , Relação Estrutura-AtividadeRESUMO
Three new polyoxygenated briarane diterpenoids, briarenols C-E (1-3), were isolated from the octocoral Briareum excavatum. The structures of briaranes 1-3 were elucidated by interpretation of spectroscopic data, and the methylenecyclohexane ring in 1 was found to exist in a twisted boat conformation. Briarenol D (2) displayed an inhibitory effect on the release of elastase by human neutrophils with an IC50 value of 4.65 µM. Briarenol E (3) was found to inhibit the protein expression of pro-inflammatory inducible nitric oxide synthase (iNOS) in a murine macrophage-like cell line, RAW 264.7, stimulated with lipopolysaccharides (LPS).
Assuntos
Antozoários/química , Diterpenos/química , Animais , Linhagem Celular , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
A new polyoxygenated briarane diterpenoid, briarenol B (1), was isolated from the octocoral Briareum excavatun and its structure determined from spectroscopic data. In RAW264.7 cells, a macrophage-like murine cell line, briarane B (1) was found to enhance the protein expression of pro-inflammatory cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS) in cells stimulated by lipopolysaccharide (LPS).