RESUMO
Antioral cancer drugs need a greater antiproliferative impact on cancer than on normal cells. Demethoxymurrapanine (DEMU) inhibits proliferation in several cancer cells, but an in-depth investigation was necessary. This study evaluated the proliferation-modulating effects of DEMU, focusing on oral cancer and normal cells. DEMU (0, 2, 3, and 4 µg/mL) at 48 h treatments inhibited the proliferation of oral cancer cells (the cell viability (%) for Ca9-22 cells was 100.0 ± 2.2, 75.4 ± 5.6, 26.0 ± 3.8, and 15.4 ± 1.4, and for CAL 27 cells was 100.0 ± 9.4, 77.2 ± 5.9, 57.4 ± 10.7, and 27.1 ± 1.1) more strongly than that of normal cells (the cell viability (%) for S-G cells was 100.0 ± 6.6, 91.0 ± 4.6, 95.0 ± 2.6, and 95.8 ± 5.5), although this was blocked by the antioxidant N-acetylcysteine. The presence of oxidative stress was evidenced by the increase of reactive oxygen species and mitochondrial superoxide and the downregulation of the cellular antioxidant glutathione in oral cancer cells, but these changes were minor in normal cells. DEMU also caused greater induction of the subG1 phase, extrinsic and intrinsic apoptosis (annexin V and caspases 3, 8, and 9), and DNA damage (γH2AX and 8-hydroxy-2-deoxyguanosine) in oral cancer than in normal cells. N-acetylcysteine attenuated all these DEMU-induced changes. Together, these data demonstrate the preferential antiproliferative function of DEMU in oral cancer cells, with the preferential induction of oxidative stress, apoptosis, and DNA damage in these cancer cells, and low cytotoxicity toward normal cells.
Assuntos
Alcaloides , Neoplasias Bucais , Humanos , Antioxidantes/farmacologia , Acetilcisteína/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio , Neoplasias Bucais/tratamento farmacológico , Apoptose , Proliferação de Células , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Indóis/farmacologia , Linhagem Celular Tumoral , Dano ao DNARESUMO
Scalarane-type sesterterpenoids are known for their therapeutic potential in cancer treatments. However, the anti-inflammatory properties of this class of metabolites remain elusive. Our current work aimed to investigate the anti-inflammatory scalaranes from marine sponge Lendenfeldia sp., resulting in the isolation of six new 24-homoscalaranes, lendenfeldaranes E-J (1-6). The structures of the new metabolites were determined by extensive spectroscopic analyses, and the absolute configuration of 1 was established by electronic circular dichroism (ECD) calculations. Compounds 2 and 3 were discovered to individually reduce the generation of superoxide anions, and compound 1 displayed an inhibitor effect on the release of elastase. These three compounds were proven to be the first anti-neutrophilic scalaranes.
Assuntos
Anti-Inflamatórios/farmacologia , Neutrófilos/efeitos dos fármacos , Poríferos/química , Sesterterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Humanos , Elastase de Leucócito/metabolismo , Estrutura Molecular , Neutrófilos/metabolismo , Via Secretória , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Relação Estrutura-Atividade , Superóxidos/metabolismoRESUMO
In the current study, an NMR spectroscopic pattern-based procedure for probing scalarane derivatives was performed and four new 24-homoscalaranes, lendenfeldaranes A-D (1- 4), along with three known compounds, 12α-acetoxy-22-hydroxy-24-methyl-24-oxoscalar-16-en- 25-al (5), felixin F (6), and 24-methyl-12,24,25-trioxoscalar-16-en-22-oic acid (7) were isolated from the sponge Lendenfeldia sp. The structures of scalaranes 1-7 were elucidated on the basis of spectroscopic analysis. Scalaranes 1-7 were further evaluated for their cytotoxicity toward a series of human cancer cell lines and the results suggested that 5 and 7 dominated in the anti- proliferative activity of the extract. The 18-aldehyde functionality was found to play a key role in their activity.
Assuntos
Proliferação de Células/efeitos dos fármacos , Poríferos/química , Sesterterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Sesterterpenos/química , Sesterterpenos/isolamento & purificaçãoRESUMO
Sepsis, an inflammatory response to infection provoked by lipopolysaccharide (LPS), is associated with high mortality, as well as ischemic stroke and new-onset atrial arrhythmia. Severe bacterial infections causing sepsis always result in profound physiological changes, including fever, hypotension, arrhythmia, necrosis of tissue, systemic multi-organ dysfunction and finally death. LPS challenge-induced inflammatory responses during sepsis may increase the likelihood of the arrhythmogenesis. Lemnalol is known to possess potent anti-inflammatory effects. This study examined whether Lemnalol (0.1 µM) could modulate the electrophysiological characteristics and calcium homeostasis of atrial myocytes under the influence of LPS (1µg/mL). Under challenge with LPS, Lemnalol-treated LA myocytes, had a longer AP duration at 20%, 50% and 90% repolarization of the amplitude, compared to the LPS-treated cells. LPS-challenged LA myocytes showed increased late sodium current, Na+-Ca2+ exchanger current, transient outward current, rapid component of delayed rectifier potassium current, tumor necrosis factor-α, NF-κB and increased phosphorylation of ryanodine receptor (RyR), but a lower L-type Ca2+ current than the control LA myocytes. Exposure to Lemnalol reversed the LPS-induced effects. The LPS-treated and control groups of LA myocytes, with or without the existence of Lemnalol. showed no apparent alterations in the sodium current amplitude or Cav1.2 expression. The expression of sarcoendoplasmic reticulum calcium transport ATPase (SERCA2) was reduced by LPS treatment, while Lemnalol ameliorated the LPS-induced alterations. The phosphorylation of RyR was enhanced by LPS treatment, while Lemnalol attenuated the LPS-induced alterations. In conclusion, Lemnalol modulates LPS-induced alterations of LA calcium homeostasis and blocks the NF-κB pathways, which may contribute to the attenuation of LPS-induced arrhythmogenesis.
Assuntos
Cálcio/metabolismo , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Citocinas/metabolismo , Átrios do Coração/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Inflamação , Lipopolissacarídeos/farmacologia , Masculino , Modelos Animais , NF-kappa B/metabolismo , Técnicas de Patch-Clamp , Coelhos , Sepse/tratamento farmacológicoRESUMO
The ubiquitin-proteasome system (UPS) is a major proteolytic pathway that safeguards protein homeostasis. The main 26S proteasome consists of a 20S catalytic core proteasome and a 19S substrate recognition proteasome. UPS dysfunction underlies many important clinical diseases involving inflammation, tumors, and neurodegeneration. Currently, three 20S proteasome inhibitors, bortezomib, carfilzomib, and ixazomib, have been approved for the treatment of multiple myeloma. We aim to screen UPS inhibitors for biomedical purposes. The protein interaction network of human cytomegalovirus UL76 targets UPS, resulting in aggregations of ubiquitinated proteins termed aggresomes. In this study, we demonstrated that cell-based high-content measurements of EGFP-UL76 aggresomes responded to bortezomib and MG132 treatment in a dose-dependent manner. Employing this high-content screening (HCS) assay, we screened natural compounds purified from Formosan soft corals. Four cembrane-based compounds, sarcophytonin A (1), sarcophytoxide (2), sarcophine (3), and laevigatol A (4), were found to enhance the high-content profiles of EGFP-UL76 aggresomes with relative ratios of 0.2. By comparison to the mechanistic action of proteasome inhibitors, compounds 1 and 3 modulated the accumulation of ubiquitinated proteins, with a unique pattern likely targeting 19S proteasome. We confirmed that the EGFP-UL76 aggresome-based HCS system greatly improves the efficacy and sensitivity of the identification of proteasome inhibitors.
Assuntos
Antozoários , Produtos Biológicos/farmacologia , Descoberta de Drogas/métodos , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Animais , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Bortezomib/farmacologia , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/farmacologia , Estudos de Viabilidade , Ensaios de Triagem em Larga Escala/métodos , Humanos , Inibidores de Proteassoma/química , Inibidores de Proteassoma/isolamento & purificação , Mapas de Interação de Proteínas/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Sensibilidade e Especificidade , Proteínas Ubiquitinadas/metabolismo , Ubiquitinação/efeitos dos fármacosRESUMO
A novel tetranorditerpenoid, sinubatin A (1) (having an unprecedented carbon skeleton), a new norditerpenoid, sinubatin B (2) (a 4,5-epoxycaryophyllene possessing an unusual methylfuran moiety side chain), and a known diterpenoid, gibberosin J (3) were isolated from soft coral Sinulariananolobata. The structures of the new compounds were elucidated by extensive analysis of spectroscopic data.
Assuntos
Antozoários/química , Terpenos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Modelos Moleculares , Estrutura Molecular , Espectrometria de Massas por Ionização por Electrospray , Espectrofotometria Infravermelho , Terpenos/isolamento & purificação , Terpenos/farmacologiaRESUMO
A novel cytotoxic diterpenoid, chabrolin A (1) (possessing an unprecedented terpenoid skeleton), as well as three new cytotoxic sesquiterpenoids, parathyrsoidins E-G (2-4), were isolated by cytotoxicity-guided fractionation from soft corals Nephtheachabroli and Paralemnalia thyrsoides. The structures of the new compounds were determined by extensive analysis of spectroscopic data.
Assuntos
Antozoários/química , Antineoplásicos/farmacologia , Terpenos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antivirais/isolamento & purificação , Antivirais/farmacologia , Linhagem Celular Tumoral , Células Cultivadas , Fracionamento Químico/métodos , Citomegalovirus/efeitos dos fármacos , Humanos , Camundongos , Estrutura Molecular , Análise Espectral/métodos , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
Blood vessels in vertebrates are established and genetically controlled in an evolutionarily-conserved manner during embryogenesis. Disruption of vascular growth by chemical compounds or environmental hormones may cause developmental defects. This study analyzed the vascular impacts of marine compound GB9 in zebrafish. GB9 was isolated from the marine soft coral Capnella imbricata and had shown anti-neuroinflammatory and anti-nociceptive activities. However, the role of GB9 on vascular development has not been reported. We first tested the survival rate of embryos under exogenous 5, 7.5, 10, and 15 µM GB9 added to the medium and determined a sub-lethal dosage of 10 µM GB9 for further assay. Using transgenic Tg(fli:eGFP) fish to examine vascular development, we found that GB9 treatment impaired intersegmental vessel (ISV) growth and caudal vein plexus (CVP) patterning at 25 hours post-fertilization (hpf) and 30 hpf. GB9 exposure caused pericardial edema and impaired circulation at 48-52 hpf, which are common secondary effects of vascular defects and suggest the effects of GB9 on vascular development. Apoptic cell death analysis showed that vascular defects were not caused by cell death, but were likely due to the inhibition of migration and/or proliferation by examining ISV cell numbers. To test the molecular mechanisms of vascular defects in GB9-treated embryos, we examined the expression of vascular markers and found the decreased expression of vascular specific markers ephrinb2, flk, mrc1, and stabilin. In addition, we examined whether GB9 treatment impairs vascular growth due to an imbalance of redox homeostasis. We found an enhanced effect of vascular defects during GB9 and H2O2 co-treatment. Moreover, exogenous N-acetyl-cysteine (NAC) treatment rescued the vascular defects in GB9 treated embryos. Our results showed that GB9 exposure causes vascular defects likely mediated by the imbalance of redox homeostasis.
Assuntos
Antozoários/química , Neovascularização Fisiológica/efeitos dos fármacos , Sesquiterpenos/farmacologia , Peixe-Zebra/embriologia , Animais , Animais Geneticamente Modificados/embriologia , Animais Geneticamente Modificados/genética , Sesquiterpenos/química , Peixe-Zebra/genéticaRESUMO
Two novel dinormonoterpenes, designated as mollisolactones A and B, were discovered from the soft coral Sinularia mollis on the basis of a chromatographic and NMR spectroscopy-based fractionation. Their structures were solved through analysis of comprehensive 1D and 2D NMR spectroscopic data and HRESIMS experiments. The biological activities of the obtained metabolites were evaluated for cytotoxicity against A-459 (human lung carcinoma), HT-29 (human colon adenocarcinoma), and P-388 (mouse lymphocytic leukemia) cancer cell lines as well as antiviral activity against HCMV (human cytomegalovirus).
Assuntos
Antozoários/química , Sesquiterpenos/química , Animais , Antozoários/metabolismo , Antivirais/química , Antivirais/isolamento & purificação , Antivirais/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citomegalovirus/efeitos dos fármacos , Células HT29 , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Monoterpenos/química , Monoterpenos/isolamento & purificação , Monoterpenos/toxicidade , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologiaRESUMO
A chromatographic and NMR spectroscopy-based fractionation on the acetone extracts of the soft coral Sinularia sandensis led to the isolation of a novel sesquiterpenoid, sandensone A (1). The structure of 1 was elucidated based on comprehensive 1D and 2D NMR spectroscopic data as well as HRESIMS spectrometry. The absolute configuration at C-12 of 1 was determined as R using a modified Mosher's method. The cytotoxicity against A549 (human lung carcinoma), HT-29 (human colon adenocarcinoma), and P-388 (mouse lymphocytic leukemia) cancer cell lines as well as antiviral activity against HCMV (human cytomegalovirus) were evaluated in vitro.
Assuntos
Antozoários/química , Sesquiterpenos/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Linhagem Celular Tumoral , Citomegalovirus , Humanos , Camundongos , Modelos MolecularesRESUMO
In recent years, several marine-derived compounds have been clinically evaluated. Diterpenes are secondary metabolites from soft coral that exhibit anti-inflammatory, anti-tumor and cytotoxic activities. In the present study, we isolated a natural diterpene product, excavatolide B, from cultured Formosan gorgonian Briareum excavatum and investigated its anti-inflammatory activities. We found that excavatolide B significantly inhibited the mRNA expression of the proinflammatory mediators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-challenged murine macrophages (RAW 264.7). We also examined the anti-inflammatory and anti-nociceptive effects of excavatolide B on intraplantar carrageenan-induced inflammatory responses. Excavatolide B was found to significantly attenuate carrageenan-induced nociceptive behaviors, mechanical allodynia, thermal hyperalgesia, weight bearing deficits and paw edema. In addition, excavatolide B inhibited iNOS, as well as the infiltration of immune cells in carrageenan-induced inflammatory paw tissue.
Assuntos
Analgésicos/farmacologia , Antozoários/química , Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Animais , Carragenina/farmacologia , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismoRESUMO
Five new polyoxygenated cembranoids, named (+)-1,15-epoxy-2-methoxy-12-methoxycarbonyl-11E-sarcophytoxide (1), (+)-2-epi-12-methoxycarbonyl-11E-sarcophine (2), 3,4-epoxyehrenberoxide A (3), ehrenbergol D (4) and ehrenbergol E (5), were obtained from the soft coral Sarcophyton ehrenbergi. The structures of 1-5 were established on the basis of comprehensive NMR and HR-ESI-MS analyses and by comparison with reported data in the literature. Compounds 4 and 5 showed moderate cytotoxicity against P-388 (mouse lymphocytic leukemia) cancer cell line with EC50 values of 2.0 and 3.0 µM, respectively. Compound 2 exhibited slight antiviral activity against HCMV (human cytomegalovirus) with IC50 values of 25.0 µg/mL.
Assuntos
Antozoários/química , Diterpenos/química , Oxigênio/química , Animais , Antozoários/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Antivirais/química , Antivirais/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Citomegalovirus/efeitos dos fármacos , Diterpenos/farmacologia , Células HT29 , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Four new cembrane-type diterpenes; numerosol A-D (1-4); along with a known steroid; gibberoketosterol (5); were isolated from the Taiwanese soft coral Sinularia numerosa. The structures of these metabolites were determined by extensive analysis of spectroscopic data. Gibberoketosterol (5) exhibited cytotoxicity against P-388 (mouse lymphocytic leukemia) cell line with an ED50 of 6.9 µM.
Assuntos
Antozoários/metabolismo , Antineoplásicos/farmacologia , Diterpenos/farmacologia , Leucemia P388/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos/química , Diterpenos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia P388/patologia , Camundongos , Esteróis/química , Esteróis/isolamento & purificação , Esteróis/farmacologia , TaiwanRESUMO
Chemical investigations on the acetone extract of the Formosan soft coral Sinularia gyrosa have obtained a novel C-4 norcembranoid possessing an unprecedented tricyclo[9.3.0.0(3,8)]tetradecane skeleton, namely sinugyrosanolide A. The NMR spectroscopic data of the novel norcembranoid were completely assigned by using a combination of 2D NMR experiments including (1)H-(1)H COSY, HSQC, HMBC, and NOESY. The cytotoxicities, anti-HCMV (human cytomegalovirus) endonuclease activities and antibacterial activities were evaluated in vitro. It showed moderate cytotoxicity against P-388 (mouse lymphocytic leukemia) cancer cell line with an EC50 of 11.8µM.
Assuntos
Antozoários/química , Antibacterianos/química , Diterpenos/química , Alcanos/química , Animais , Antozoários/metabolismo , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Carbono/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citomegalovirus/enzimologia , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Endonucleases/antagonistas & inibidores , Endonucleases/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Camundongos , Conformação Molecular , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/metabolismoRESUMO
Two new kelsoane-type sesquiterpenes, namely kelsoenethiol (1) and dikelsoenyl ether (2), were obtained from the Formosan soft coral Nephthea erecta. Their structures were elucidated through extensive spectroscopic analyses, ESI orbitrap mass and quantum chemical calculations (QCC). The cytotoxicity against A-459 (human lung carcinoma), P-388 (mouse lymphocytic leukemia), and HT-29 (human colon adenocarcinoma) cancer cell lines of 1 and 2 was evaluated in vitro. Compound 1 showed cytotoxicity against P-388 and HT-29 cells with ED50s of 1.3 and 1.8 µg/mL, respectively.
Assuntos
Antozoários , Sesquiterpenos/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células HT29 , Humanos , Leucemia P388 , Camundongos , Sesquiterpenos/isolamento & purificaçãoRESUMO
Continuing chemical investigation on the acetone extracts of the soft coral Sarcophyton ehrenbergi collected off the coast of San-hsian-tai, Taitong County, Taiwan led to the isolation of two new diterpenoids, ehrenbergol C and acetyl ehrenberoxide B (1 and 2). The structures of these isolated metabolites were elucidated through extensive spectroscopic analyses. Moreover, in vitro tests show that compounds 1 and 2 displayed antiviral activity towards human cytomegalovirus, with EC50 of 20 and 8.0 µg/mL, respectively.
Assuntos
Antozoários/química , Diterpenos/química , Animais , Antivirais/química , Antivirais/farmacologia , Citomegalovirus/efeitos dos fármacos , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Análise Espectral/métodos , TaiwanRESUMO
Four new nardosinane-type sesquiterpenoids, parathyrsoidins A-D (1-4) were isolated from the soft coral Paralemnalia thyrsoides. The structures of parathyrsoidins A-D (1-4) were determined by extensive spectral analysis and their cytotoxicity against selected cancer cell lines as well as antiviral activity against human cytomegalovirus (HCMV) were evaluated in vitro.
Assuntos
Antozoários/química , Fatores Biológicos/química , Sesquiterpenos/química , Animais , Antivirais/química , Antivirais/farmacologia , Fatores Biológicos/farmacologia , Linhagem Celular Tumoral , Citomegalovirus/efeitos dos fármacos , Humanos , Estrutura MolecularRESUMO
A new cytotoxic 19-oxygenated steroid, nebrosteroid Q(1) and two new cytotoxic 19-norergosterols, nebrosteroids R and S (2 and 3) were isolated from the soft coral Nephthea chabrolii collected at San-Hsian-Tai. The structures of nebrosteroids Q-S (1-3) were elucidated by spectral analysis, and their cytotoxicity against selected cancer cells as well as antiviral activity against human cytomegalovirus (HCMV) were measured in vitro.
Assuntos
Antozoários/metabolismo , Esteroides/metabolismo , Animais , Antozoários/química , Antivirais/química , Antivirais/farmacologia , Linhagem Celular , Humanos , Modelos Moleculares , Estrutura Molecular , Esteroides/químicaRESUMO
An acute gout attack manifests in the joint as dramatic inflammation. To date, the clinical use of medicinal agents has typically led to undesirable side effects. Numerous efforts have failed to create an effective and safe agent for the treatment of gout. Lemnalol-an extract from Formosan soft coral-has documented anti-inflammatory and anti-nociceptive properties. In the present study, we attempt to examine the therapeutic effects of lemnalol on intra-articular monosodium urate (MSU)-induced gouty arthritis in rats. In the present study, we found that treatment with lemnalol (intramuscular [im]), but not colchicine (oral [po]), significantly attenuated MUS-induced mechanical allodynia, paw edema and knee swelling. Histomorphometric and immunohistochemistry analysis revealed that MSU-induced inflammatory cell infiltration, as well as the elevated expression of c-Fos and pro-inflammatory proteins (inducible nitric oxide synthase and cyclooxygenase-2) observed in synovial tissue, were significantly inhibited by treatment with lemnalol. We conclude that lemnalol may be a promising candidate for the development of a new treatment for gout and other acute neutrophil-driven inflammatory diseases.
Assuntos
Artrite Gotosa/tratamento farmacológico , Ciclo-Oxigenase 2/biossíntese , Leucócitos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/biossíntese , Proteínas Proto-Oncogênicas c-fos/biossíntese , Sesquiterpenos/farmacologia , Animais , Antozoários/química , Anti-Inflamatórios/farmacologia , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/imunologia , Artrite Gotosa/metabolismo , Colchicina/farmacologia , Ciclo-Oxigenase 2/metabolismo , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Wistar , Sesquiterpenos/química , Ácido ÚricoRESUMO
In the continued search for novel bioactive substances from the Taiwanese octocoral Briareum excavatum collected at Orchid Island, three new briarane-type diterpenoids, briacavatolides D-F (1-3) were isolated from the acetone extract. The structures of these compounds were elucidated by extensive NMR spectroscopic analysis and physical data. The anti-HCMV (human cytomegalovirus) activity of 1-3 and their cytotoxicity against selected cancer cell lines were evaluated.