RESUMO
Continuing chemical investigation of the Red Sea sponge Spongia sp. led to the isolation of four new 3,4-seco-3,19-dinorspongian diterpenoid lactones, secodinorspongins A-D (1-4), along with a classical spongian diterpenoid lactone, sponginolide (5). The chemical structures, including the absolute configurations of these compounds, were elucidated using the extensive spectroscopic study composed of 1D and 2D NMR data analyses, and a comparison between calculated-electronic-circular-dichroism (ECD) and experimental-circular-dichroism (CD) spectra. A plausible biosynthetic pathway of 1-4 was also proposed. Furthermore, the cytotoxicity, antibacterial and anti-inflammatory activities of 1-5 were evaluated. Compound 1 was found to exhibit inhibitory activity against the growth of Staphylococcus aureus (S. aureus), and 4 and 5 exhibited suppression of superoxide-anion generation and elastase release in fMLF/CB-induced human neutrophils.
Assuntos
Diterpenos , Poríferos , Animais , Humanos , Lactonas , Staphylococcus aureus , Estrutura Molecular , Poríferos/química , Diterpenos/químicaRESUMO
The present chemical investigation on the organic extract of the soft coral Sarcophyton cinereum has contributed to the isolation of four new cembranoids: 16ß- and 16α-hydroperoxyisosarcophytoxides (1 and 2), 16ß- and 16α-methoxyisosarcophytoxides (3 and 4), and a known cembranoid, lobocrasol (5). The structures of all isolates were elucidated by detailed spectroscopic analysis. Their structures were characterized by a 2,5-dihydrofuran moiety, of which the relative configuration was determined by DU8-based calculation for long-range coupling constants (4JH,H). The cytotoxicity and immunosuppressive activities of all isolates were evaluated in this study.
Assuntos
Antozoários , Diterpenos , Animais , Antozoários/química , Diterpenos/química , Estrutura MolecularRESUMO
A polyoxygenated and halogenated labdane, spongianol (1); a polyoxygenated steroid, 3ß,5α,9α-trihydroxy-24S-ethylcholest-7-en-6-one (2); a rare seven-membered lactone B ring, (22E,24S)-ergosta-7,22-dien-3ß,5α-diol-6,5-olide (3); and an α,ß-unsaturated fatty acid, (Z)-3-methyl-9-oxodec-2-enoic acid (4) as well as five known compounds, 10-hydroxykahukuene B (5), pacifenol (6), dysidamide (7), 7,7,7-trichloro-3-hydroxy-2,2,6-trimethyl-4-(4,4,4-trichloro-3-methyl-1-oxobu-tylamino)-heptanoic acid methyl ester (8), and the primary metabolite 2'-deoxynucleoside thymidine (9), have been isolated from the Red Sea sponge Spongia sp. The stereoisomer of 3 was discovered in Ganoderma resinaceum, and metabolites 5 and 6, isolated previously from red algae, were characterized unprecedentedly in the sponge. Compounds 7 and 8 have not been found before in the genus Spongia. Compounds 1-9 were also assayed for cytotoxicity as well as antibacterial and anti-inflammatory activities.
Assuntos
Poríferos , Animais , Antibacterianos/química , Anti-Inflamatórios/química , Oceano Índico , Estrutura Molecular , Poríferos/química , Esteroides/químicaRESUMO
Three new 5,5,6,6,5-pentacyclic spongian diterpenes, spongenolactones A-C (1-3), were isolated from a Red Sea sponge Spongia sp. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and the absolute configurations of 1-3 were determined on the basis of comparison of the experimental circular dichroism (CD) and calculated electronic circular dichroism (ECD) spectra. Compounds 1-3 are the first 5,5,6,6,5-pentacyclic spongian diterpenes bearing an ß-hydroxy group at C-1. These metabolites were assayed for their cytotoxic, antibacterial, and anti-inflammatory activities. All three compounds were found to exert inhibitory activity against superoxide anion generation in fMLF/CB-stimulated human neutrophils. Furthermore, 1 showed a higher activity against the growth of Staphylococcus aureus in comparison to 2.
Assuntos
Diterpenos , Poríferos , Animais , Diterpenos/química , Humanos , Oceano Índico , Estrutura Molecular , Staphylococcus aureusRESUMO
Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone (1), a carboxylic acid, spongiafuranic acid A (2), one hydroxamic acid, spongiafuranohydroxamic acid A (3), and a furanyl trinorsesterpenoid 16-epi-irciformonin G (4), along with three known metabolites (-)-sponalisolide B (5), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one (6), and cholesta-7-ene-3ß,5α-diol-6-one (7). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 µM, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.
Assuntos
Anti-Inflamatórios/metabolismo , Diterpenos/metabolismo , Poríferos/metabolismo , Terpenos/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Células Cultivadas , Diterpenos/química , Diterpenos/farmacologia , Humanos , Oceano Índico , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Poríferos/química , Terpenos/química , Terpenos/farmacologiaRESUMO
Two new capnosane-based diterpenoids, flaccidenol A (1) and 7-epi-pavidolide D (2), two new cembranoids, flaccidodioxide (3) and flaccidodiol (4), and three known compounds 5 to 7 were characterized from the marine soft coral Klyxum flaccidum, collected off the coast of the island of Pratas. The structures of the new compounds were determined by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, and spectroscopic data comparison with related structures. The rare capnosane diterpenoids were isolated herein from the genus Klyxum for the first time. The cytotoxicity of compounds 1 to 7 against the proliferation of a limited panel of cancer cell lines was assayed. The isolated diterpenoids also exhibited anti-inflammatory activity through suppression of superoxide anion generation and elastase release in the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-stimulated human neutrophils. Furthermore, 1 and 7 also exhibited cytotoxicity toward the tested cancer cells, and 7 could effectively inhibit elastase release. It is worth noting that the biological activities of 7 are reported for the first time in this paper.
Assuntos
Antozoários/química , Fatores Biológicos/farmacologia , Diterpenos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocalasina B/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Humanos , Espectroscopia de Ressonância Magnética/métodos , N-Formilmetionina Leucil-Fenilalanina/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Superóxidos/metabolismoRESUMO
Three new polyoxygenated steroids, michosterols A-C (1-3), and four known compounds (4-7) were isolated from the ethyl acetate (EtOAc) extract of the soft coral Lobophytum michaelae, collected off the coast of Taitung. The structures of the new compounds were elucidated on the basis of spectroscopic analyses and comparison of the nuclear magnetic resonance (NMR) data with related steroids. The cytotoxicity of compounds 1-3 against the proliferation of a limited panel of cancer cell lines was assayed. Compound 1 was found to display moderate cytotoxicity against adenocarcinomic human alveolar basal epithelial (A549) cancer cells. It also exhibited potent anti-inflammatory activity by suppressing superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-stimulated human neutrophils. Furthermore, 3 could effectively inhibit elastase release, as well.
Assuntos
Antozoários/química , Anti-Inflamatórios/química , Esteroides/química , Células A549 , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citocalasina B/farmacologia , Citotoxinas/química , Citotoxinas/farmacologia , Humanos , Espectroscopia de Ressonância Magnética/métodos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Esteroides/farmacologia , Superóxidos/metabolismoRESUMO
Three new eunicellin-type diterpenoids, krempfielins N-P (1-3), were isolated from a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compound 3 exhibited activity to inhibit superoxide anion generation. Both 1 and 3, in particular 1, were shown to display significant anti-inflammatory activity by inhibiting the elastase release in FMLP/CB-induced human neutrophils.
Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Neutrófilos/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Citocalasina B/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Análise Espectral , TaiwanRESUMO
Five new eunicellin-based diterpenoids, klymollins T-X (1-5), along with two known compounds (6 and 7) have been isolated from the soft coral Klyxum molle. The structures of these new metabolites were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. Compound 5 was found to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. Furthermore, compounds 4 and 7 were shown to exhibit cytotoxicity against a limited panel of human cancer cell lines.
Assuntos
Antozoários/química , Diterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Diterpenos/química , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Modelos MolecularesRESUMO
Two new eunicellin-based diterpenoids, krempfielins Q and R (1 and 2), and one known compound cladieunicellin K (3) have been isolated from a Formosan soft coral Cladiella krempfi. The structures of these two new metabolites were elucidated by extensive spectroscopic analysis. Anti-inflammatory activity of new metabolites to inhibit the superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (FMLP/CB)-induced human neutrophil cells and cytotoxicity of both new compounds toward five cancer cell lines were reported.
Assuntos
Antozoários/química , Diterpenos/farmacologia , Animais , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Diterpenos/química , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Superóxidos/metabolismoRESUMO
New four eunicellin-based diterpenoids, krempfielins J-M (1-4) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis. The structure of compound 2 is rare due to the presence of the highly oxygenated pattern. Anti-inflammatory activity of 1-6 to inhibit the superoxide anion generation and elastase release in FMLP/CB-induced human neutrophils was also evaluated, and 2 and 4 were shown to possess the ability to inhibit the elastase release.
Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Neutrófilos/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Citocalasina B/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Inflamação/tratamento farmacológico , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Análise Espectral , Superóxidos/metabolismoRESUMO
Five new eunicellin-based diterpenoids, krempfielins E-I (1-5) and seven known compounds (6-12) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis. Metabolites 5, 6, 10 and 12 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 6 and 10 could potently inhibit the accumulation of the pro-inflammatory iNOS protein, and 6 and 12 could significantly reduce the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.
Assuntos
Antozoários/metabolismo , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Diterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Inflamação/tratamento farmacológico , Inflamação/patologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Análise Espectral , TaiwanRESUMO
Four new eunicellin-based diterpenes, simplexins P-S (1-4), and the known compound simplexin A (5), have been isolated from the soft coral Klyxum simplex. The structures of the new metabolites were determined on the basis of extensive spectroscopic analysis, particularly 1D and 2D NMR experiments. Compounds 1 and 3-5 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines, 3 being the most cytotoxic.
Assuntos
Antozoários/química , Diterpenos/química , Diterpenos/farmacologia , Terpenos/química , Terpenos/farmacologia , Animais , Linhagem Celular Tumoral , Humanos , Células K562 , Espectroscopia de Ressonância Magnética/métodosRESUMO
Four new eunicellin-based diterpenoids, krempfielins A-D (1-4), along with two known compounds (5 and 6) have been isolated from a soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compounds 5 and 6 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 2, 3, 5 and 6 were shown to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells.