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
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
The new asperorlactone (1), along with the known illudalane sesquiterpene echinolactone D (2), two known pyrones, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (3) and its acetate 4, and 4-hydroxybenzaldehyde (5), were isolated from a culture of Aspergillus oryzae, collected from Red Sea marine sediments. The structure of asperorlactone (1) was elucidated by HR-ESIMS, 1D, and 2D NMR, and a comparison between experimental and DFT calculated electronic circular dichroism (ECD) spectra. This is the first report of illudalane sesquiterpenoids from Aspergillus fungi and, more in general, from ascomycetes. Asperorlactone (1) exhibited antiproliferative activity against human lung, liver, and breast carcinoma cell lines, with IC50 values < 100 µM. All the isolated compounds were also evaluated for their toxicity using the zebrafish embryo model.
Assuntos
Aspergillus oryzae/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/toxicidade , Animais , Organismos Aquáticos/química , Ascomicetos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Fungos/química , Sedimentos Geológicos , Humanos , Oceano Índico , Concentração Inibidora 50 , Células MCF-7 , Estrutura Molecular , Sesquiterpenos Policíclicos , Peixe-ZebraRESUMO
Three new polyoxygenated diterpenoids with a rare 4-isopropyl-1,5,8a-trimethylperhydrophenanthrane structure of the klysimplexane skeleton, briarols AâC (1â3), and one eunicellin-based diterpenoid, briarol D (4), were isolated from Briareum violaceum, a gorgonian inhabiting Taiwanese waters. The chemical structures of these compounds were determined by employing extensive analyses of NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. Metabolites 1â3 were found to possess the rarely found skeleton of the diterpenoid klysimplexin T. All isolated compounds showed very weak cytotoxic activity against the growth of three cancer cell lines. A plausible biosynthetic pathway for briarols AâC from the coexisting eunicellin diterpenoid briarol D (4) was postulated.
Assuntos
Antozoários/metabolismo , Diterpenos/química , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Química Farmacêutica/métodos , Desenho de Fármacos , Células HT29 , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Neoplasias/tratamento farmacológico , Pós , Prótons , Espectrometria de Massas por Ionização por Electrospray , Taiwan , Poluentes Químicos da Água/análise , Purificação da ÁguaRESUMO
Four new aromatic polyketides (1-4) were isolated from Penicillium sp. RO-11, obtained from the sediment of a hydrothermal spring in the southwestern region of Saudi Arabia. The new compounds are penipyranicins A-C (1-3), characterized by a 4-methyl-4H-pyran moiety, a structural motif unprecedented among fungal polyketides, and the naphthopyrone derivative isopyrenulin (4). The structures of the new compounds were elucidated on the basis of data from mass spectrometry, 1D and 2D NMR analysis, and comparison between experimental and time-dependent density functional theory-calculated electronic circular dichroism spectra. A plausible biosynthetic pathway connecting penipyranicins and isopyrenulin is proposed. The isolated compounds were active against Gram-positive and Gram-negative bacteria.
Assuntos
Antibacterianos/isolamento & purificação , Penicillium/isolamento & purificação , Policetídeos/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Fermentação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Estrutura Molecular , Penicillium/química , Policetídeos/química , Policetídeos/farmacologia , Análise Espectral/métodosRESUMO
The present investigation on chemical constituents of the soft coral Sarcophyton cherbonnieri resulted in the isolation of seven new cembranoids, cherbonolides F-L (1-7). The chemical structures of 1-7 were determined by spectroscopic methods, including infrared, one- and two-dimensional (1D and 2D) NMR (COSY, HSQC, HMBC, and NOESY), MS experiments, and a chemical reduction of hydroperoxide by triphenylphosphine. The anti-inflammatory activities of 1-7 against neutrophil proinflammatory responses were evaluated by measuring their inhibitory ability toward N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced superoxide anion generation and elastase release in primary human neutrophils. The results showed that all isolates exhibited moderate activities, while cherbonolide G (2) and cherbonolide H (3) displayed a more active effect than others on the inhibition of elastase release (48.2% ± 6.2%) and superoxide anion generation (44.5% ± 4.6%) at 30 µM, respectively.
Assuntos
Antozoários/metabolismo , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Neutrófilos/efeitos dos fármacos , Adulto , Animais , Anti-Inflamatórios/isolamento & purificação , Diterpenos/isolamento & purificação , Humanos , Elastase de Leucócito/metabolismo , Estrutura Molecular , Neutrófilos/enzimologia , Relação Estrutura-Atividade , Superóxidos/metabolismo , Adulto JovemRESUMO
Further chemical investigation of the EtOAc extract of the soft coral Lobophytum varium resulted in the discovery of eleven new diterpenoids lobovarols F-P (1-11) of lobane- and prenyleudesmane-types, along with two known metabolites (12 and 13). The structures of the new metabolites were established by spectroscopic analyses, including 2D NMR experiments. The absolute configuration of 1 was determined using Mosher's method. The complete assignment of 1H and 13C NMR spectroscopic data of 12 and 13 and the identification of pyran-derived moieties in the prenyleudesmanes were reported for the first time. Anti-inflammatory activities of the isolated compounds in suppressing elastase release and superoxide anion generation in human neutrophils were disclosed for 1, 2, 4, 12, and 13. A stereospecific biosynthesis for lobanes and prenyleudesmanes from the related prenylgermacranes could explain the coexistence of lobanes and prenylgermacranes in L. varium.
Assuntos
Antozoários/química , Anti-Inflamatórios/isolamento & purificação , Diterpenos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Estereoisomerismo , Superóxidos/metabolismoRESUMO
Three new eunicellin-derived diterpenoids of briarellin type, briarenones AâC (1â3), were isolated from a Formosan gorgonian Briareum violaceum. The chemical structures of the compounds were elucidated on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR. The absolute configuration of 1 was further confirmed by a single crystal X-ray diffraction analysis. The in vitro cytotoxic and anti-inflammatory potentialities of the isolated metabolites were tested against the growth of a limited panel of cancer cell lines and against the production of superoxide anions and elastase release in N-formyl-methionyl-leucyl-phenyl-alanine and cytochalasin B (fMLF/CB)-stimulated human neutrophils, respectively.
Assuntos
Cnidários/química , Diterpenos/química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Citocalasinas/farmacologia , Diterpenos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Conformação Molecular , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Superóxidos/metabolismo , Difração de Raios XRESUMO
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
Six new cembranoids, cherbonolides A-E (1â»5) and bischerbolide peroxide (6), along with one known cembranoid, isosarcophine (7), were isolated from the Formosan soft coral Sarcophyton cherbonnieri. The structures of these compounds were elucidated by detailed spectroscopic analysis and chemical methods. Compound 6 was discovered to be the first example of a molecular skeleton formed from two cembranoids connected by a peroxide group. Compounds 1â»7 were shown to have the ability of inhibiting the production of superoxide anions and elastase release in N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLF/CB)-induced human neutrophils.
Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Neutrófilos/efeitos dos fármacos , Peróxidos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular Tumoral , Citocalasina B/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Humanos , Estrutura Molecular , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Peróxidos/química , Peróxidos/isolamento & purificação , Superóxidos/metabolismoRESUMO
Six new polyoxygenated cembrane-based diterpenoids, stellatumolides Aâ»C (1â»3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7â»16) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum. The structures of the new compounds were established by extensive spectroscopic analyses, including 1D and 2D nuclear magnetic resonance (NMR) spectroscopy and data comparison with related structures. Compounds 8 and 14 were isolated from a natural source for the first time. The isolated metabolites were shown to be not cytotoxic against a limited panel of cancer cells. Compound 9 showed anti-inflammatory activity by reducing the expression of proinflammatory cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins in lipopolysaccharide (LPS)-stimulated mouse leukaemic monocyte macrophage (RAW 264.7) cells.
Assuntos
Antozoários/química , Inibidores de Ciclo-Oxigenase 2/química , Diterpenos/química , Animais , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/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
Extensive phytochemical analysis of different root fractions of Jatropha pelargoniifolia Courb. (Euphorbiaceae) has resulted in the isolation and identification of 22 secondary metabolites. 6-hydroxy-8-methoxycoumarin-7-O-ß-d-glycopyranoside (15) and 2-hydroxymethyl N-methyltryptamine (18) were isolated and identified as new compounds along with the known diterpenoid (1, 3, 4, and 7), triterpenoid (2 and 6), flavonoid (5, 11, 13, 14, and 16), coumarinolignan (8â»10), coumarin (15), pyrimidine (12), indole (17, 18), and tyramine-derived molecules (19â»22). The anti-inflammatory, analgesic, and antipyretic activities were evaluated for fifteen of the adequately available isolated compounds (1â»6, 8â»11, 13, 14, 16, 21, and 22). Seven (4, 6, 10, 5, 13, 16, and 22) of the tested compounds showed a significant analgesic effect ranging from 40% to 80% at 10 mg/kg in two in vivo models. Compound 1 could also prove its analgesic property (67.21%) when it was evaluated on a third in vivo model at the same dose. The in vitro anti-inflammatory activity was also recorded where all compounds showed the ability to scavenge nitric oxide (NO) radical in a dose-dependent manner. However, eight compounds (1, 4, 5, 6, 10, 13, 16, and 22) out of the fifteen tested compounds exhibited considerable in vivo anti-inflammatory activity which reached 64.91% for compound 10 at a dose of 10 mg/kg. Moreover, the tested compounds exhibited an antipyretic effect in a yeast-induced hyperthermia in mice. The activity was found to be highly pronounced with compounds 1, 5, 6, 10, 13, and 16 which decreased the rectal temperature to about 37 °C after 2 h of the induced hyperthermia (~39 °C) at a dose of 10 mg/kg. This study could provide scientific evidence for the traditional use of J. pelargoniifolia as an anti-inflammatory, analgesic, and antipyretic.
Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Antipiréticos/farmacologia , Jatropha/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Analgésicos/química , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antipiréticos/química , Antipiréticos/isolamento & purificação , Monoaminas Biogênicas/química , Monoaminas Biogênicas/isolamento & purificação , Monoaminas Biogênicas/farmacologia , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Edema/tratamento farmacológico , Edema/fisiopatologia , Febre/tratamento farmacológico , Febre/fisiopatologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Hipertermia Induzida/métodos , Indóis/química , Indóis/isolamento & purificação , Indóis/farmacologia , Jatropha/metabolismo , Masculino , Camundongos , Óxido Nítrico/antagonistas & inibidores , Dor/tratamento farmacológico , Dor/fisiopatologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Pirimidinas/química , Pirimidinas/isolamento & purificação , Pirimidinas/farmacologia , Ratos , Ratos Wistar , Metabolismo Secundário , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
Continuing study of the ethyl acetate (EtOAc) extract of the cultured soft coral Sinularia brassica afforded five new withanolides, sinubrasolides H-L (1-5). The structures of the new compounds were elucidated on the basis of spectroscopic analysis. The cytotoxicities of new compounds 1-5 and a known compound sinubrasolide A (6) against the proliferation of a limited panel of cancer cell lines were assayed. The anti-inflammatory activities of compounds 1-6 were evaluated by measuring their ability to suppress N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils.
Assuntos
Antozoários/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Vitanolídeos/química , Vitanolídeos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Citocalasina B/imunologia , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Neutrófilos/efeitos dos fármacos , Elastase Pancreática/imunologia , Superóxidos/imunologia , Vitanolídeos/isolamento & purificaçãoRESUMO
New cembranoids klyflaccicembranols A-I (1-9), along with gibberosene D (10), have been isolated from the organic extract of a Formosan soft coral Klyxum flaccidum. Their structures were established by extensive spectroscopic analyses, including 2D NMR spectroscopy, and spectral data comparison with related structures. The cytotoxicity of the isolated metabolites, as well as their nitric oxide (NO) inhibitory activity, were evaluated and reported. Metabolites 2, 4, 6, 8 and 9 were found to exhibit variable activities against a limited panel of cancer cell lines in a range of IC50 16.5-49.4 µM. Among the tested cembranoids, compounds 4, 5, 6, and 9 significantly inhibited NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages at a dose of 50 µg/mL.
Assuntos
Antozoários/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Células A549 , Animais , Linhagem Celular Tumoral , Carvão Mineral , Ensaios de Seleção de Medicamentos Antitumorais , Células HT29 , Humanos , Células K562 , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Camundongos , Óxido Nítrico/metabolismoRESUMO
New lobane-based diterpenoids lobovarols A-D (1-4) and a prenyleudesmane-type diterpenoid lobovarol E (5) along with seven known related diterpenoids (6-12) were isolated from the ethyl acetate extract of a Taiwanese soft coral Lobophytum varium. Their structures were identified on the basis of multiple spectroscopic analyses and spectral comparison. The absolute configuration at C-16 of the known compound 11 is reported herein for the first time. The anti-inflammatory activities of compounds 1-12 were assessed by measuring their inhibitory effect on N-formyl-methionyl-leucyl-phenyl-alanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release in human neutrophils. Metabolites 2, 5, and 11 were found to show moderate inhibitory activity on the generation of superoxide anion, while compounds 5, 8, 11, and 12 could effectively suppress elastase release in fMLP/CB-stimulated human neutrophil cells at 10 µM. All of the isolated diterpenoids did not exhibit cytotoxic activity (IC50 > 50 µM) towards a limited panel of cancer cell lines.
Assuntos
Antozoários/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Linhagem Celular Tumoral , Citocalasina B/farmacologia , Diterpenos/química , Humanos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Elastase Pancreática/metabolismo , Superóxidos/metabolismoRESUMO
Five new isoprenoids, 3,4,8,16-tetra-epi-lobocrasol (1), 1,15ß-epoxy-deoxysarcophine (2), 3,4-dihydro-4α,7ß,8α-trihydroxy-Δ²-sarcophine (3), ent-sarcophyolide E (4), and 16-deacetyl- halicrasterol B (5) and ten known compounds 6â15, were characterized from the marine soft coral Sarcophyton glaucum, collected off Taitung coastline. Their structures were defined by analyzing spectra data, especially 2D NMR and electronic circular dichroism (ECD). The structure of the known compound lobocrasol (7) was revised. Cytotoxicity potential of the isolated compounds was reported, too.
Assuntos
Antozoários/química , Antineoplásicos/isolamento & purificação , Terpenos/isolamento & purificação , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dicroísmo Circular , Humanos , Espectroscopia de Ressonância Magnética , Terpenos/química , Terpenos/farmacologiaRESUMO
Onion peel is a common bio-waste, occasionally used in traditional medicine in treatment of liver ailment and inflammation. However, a phytochemical and biological study is further required to provide the scientific evidence for this use. A phenolic-rich extract of red onion peels (coded as ACPE) was primarily prepared and then subjected to chromatographic separation. From the extract, six phenolic antioxidant compounds along with two phytosterols were isolated and identified by means of spectroscopic (NMR and MS) analyses. The in vivo protective activity of the ACPE against the oxidative stress induced by carbon tetrachloride (CCl4) free radicals, in liver and kidney, was assessed in rats. Relative to the CCl4-challenged animals, pre-treatment with ACPE could significantly ameliorate the hepatonephrolinked serum and tissue markers in a dose-dependent response. The flavonol- and phenolic acid-based nature of constituents, the high phenolic content (72.33±5.30 mg gallic acid equivalent per one gram) and the significant antioxidant capacity (>1/3 potency of rutin) of ACPE may be thus attributed strongly to the hepatonephro-protective and anti-inflammatory effect of ACPE. The results suggest that red onion peels can serve as a convenient and cost-effective source of high-value antioxidant nutraceuticals for protection against oxidative stress-related disorders.