RESUMO
Metastasis occurs when cancer cells detach from a tumor, travel to distant sites in the body and develop into tumors in these new locations. Most cancer patients die from metastases. Among the various forms of cancer metastasis, lymphatic metastasis is an important determinant in cancer treatment and staging. In this study, we investigated lymphangiogenesis inhibitors from crude drugs used in Japan and Korea. The three crude drugs Saussureae Radix, Psoraleae Semen and Aurantti Fructus Immaturus significantly inhibited the proliferation of temperature-sensitive rat lymphatic endothelial (TR-LE) cells in vitro. By a chromatographic method using bioassay-guided fractionation methods, costunolide (1) and dehydrocostus lactone (2) from S. Radix, p-hydroxybenzaldehyde (3), psoralen (4), angelicin (5), psoracorylifol D (6), isobavachalone (7), bavachinin (8) Δ(3),2-hydroxybakuchiol (9) and bakuchiol (10) from P. Semen and cis-octadecyl ferulate (11), (2R)-3ß,7,4'-trihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (12), (2S)-7,4'-dihydroxy-5-methoxy-8-(γ,γ-dimethylallyl)-flavanone (13) and umbelliferone (14) from A. F. Immaturus were obtained. Three compounds (compounds 11-13) from A. F. Immaturus were isolated for the first time from this medicinal plant. Among isolated compounds, ten compounds (compounds 1, 2, 6-12, 13) showed an inhibitory effect on the proliferation and the capillary-like tube formation of TR-LE cells. In addition, all compounds except compound 12 showed selective inhibition of the proliferation of TR-LE cells compared to Hela and Lewis lung carcinoma (LLC) cells. These compounds might offer clinical benefits as lymphangiogenesis inhibitors and may be good candidates for novel anti-cancer and anti-metastatic agents.
Assuntos
Inibidores da Angiogênese/farmacologia , Extratos Vegetais/farmacologia , Poncirus , Psoralea , Saussurea , Animais , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Frutas , Células HeLa , Humanos , Japão , Linfangiogênese/efeitos dos fármacos , Raízes de Plantas , Ratos , República da Coreia , SementesRESUMO
Four new cembrane diterpenes (1-4) and fifteen known cembranoids (5-19) were isolated from an Okinawan soft coral Lobophytum crassum. The structures of these four new cembranoids were determined on the basis of spectroscopic evidence. In particular, the absolute stereochemistry of 1, 2, 5 and 6 were elucidated by the application of the modified Mosher's method and circular dichroism (CD) spectral data. The inhibitory effects of some isolates were evaluated on nitric oxide (NO) production against a murine macrophage-like cell line (Raw 264.7). Cembranoids consisting of alpha-methylene-gamma-lactone, exhibited the significant effect on NO production.
Assuntos
Antozoários/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Diterpenos/química , Diterpenos/farmacologia , Óxido Nítrico/antagonistas & inibidores , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , Diterpenos/isolamento & purificação , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico/imunologiaRESUMO
The close association of inflammation, angiogenesis and cancer progression is now highlighted, and in this study we especially focused on a close association of inflammation and lymphangiogenesis. We found that proinflammatory cytokine, interleukin-1beta (IL-1beta), could induce lymphangiogenesis in mouse cornea through enhanced production of potent lymphangiogenic factors, VEGF-A, VEGF-C and VEGF-D. IL-1beta-induced lymphangiogenesis, but not angiogenesis, was inhibited by administration of a selective anti-VEGF receptor-3 (VEGFR-3) neutralizing antibody. And in mouse cornea we observed recruitment of monocyte/macrophages and neutrophils by IL-1beta implanted cornea. Depletion of macrophages by a bisphosphonate encapsulated in liposomes inhibited this IL-1beta-induced lymphangiogenesis and also up-regulation of VEGF-A, VEGF-C, and VEGF-D. Furthermore, IL-1beta-induced lymphangiogenesis and angiogenesis were suppressed by NF-kappaB inhibition with marked suppression of VEGF-A, VEGF-C, and VEGF-D expression.
Assuntos
Interleucina-1beta/imunologia , Ceratite/imunologia , Linfangiogênese/imunologia , Macrófagos/imunologia , NF-kappa B/metabolismo , Fator C de Crescimento do Endotélio Vascular/biossíntese , Fator D de Crescimento do Endotélio Vascular/biossíntese , Animais , Proliferação de Células , Córnea/irrigação sanguínea , Córnea/efeitos dos fármacos , Córnea/imunologia , Difosfonatos/farmacologia , Fator 2 de Crescimento de Fibroblastos/biossíntese , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/farmacologia , Humanos , Interleucina-1beta/farmacologia , Linfangiogênese/efeitos dos fármacos , Linfangiogênese/genética , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/agonistas , NF-kappa B/antagonistas & inibidores , Neovascularização Patológica/imunologia , Fator C de Crescimento do Endotélio Vascular/genética , Fator C de Crescimento do Endotélio Vascular/farmacologia , Fator D de Crescimento do Endotélio Vascular/genética , Fator D de Crescimento do Endotélio Vascular/farmacologiaRESUMO
A new monomethylated ganglioside, DSG-A (3), was obtained, together with four known gangliosides, compounds (1, 2, 4, 5), from the lipid fraction of the chloroform/methanol extract of the ovary of the sea urchin Diadema setosum. The structures of the new ganglioside was determined on the basis of chemical and spectroscopic evidence to be 1-O-[9-O-methyl-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3). The ceramide moiety of 3 was composed of C18-phytosphingosine base, and 2-hydroxy and nonhydroxylated fatty acid units. These gangliosides showed neuritogenic activity toward the rat pheochromocytoma cell line PC-12 in the presence of nerve growth factor, in which compound 3 showed the most potent activity.
Assuntos
Gangliosídeos/farmacologia , Neuritos/efeitos dos fármacos , Ovário/química , Animais , Configuração de Carboidratos , Sequência de Carboidratos , Proliferação de Células/efeitos dos fármacos , Feminino , Gangliosídeos/química , Cromatografia Gasosa-Espectrometria de Massas , Metanol/química , Metilação , Dados de Sequência Molecular , Células PC12 , Ratos , Ouriços-do-Mar , Solventes , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Infravermelho , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The effects of the gangliosides isolated from echinoderms on the neuritogenesis of a rat pheochromocytoma cell line (PC-12 cells) in the presence of nerve growth factor were investigated. The results show that they displayed neuritogenic activity. Based on the observed results, a structure-activity relationship has been established.
Assuntos
Equinodermos/química , Gangliosídeos/química , Gangliosídeos/farmacologia , Animais , Estrutura Molecular , Fator de Crescimento Neural/farmacologia , Células PC12 , Feocromocitoma/tratamento farmacológico , Ratos , Relação Estrutura-AtividadeRESUMO
Three new disialo- and trisialo-gangliosides, CEG-6 (6), CEG-8 (8), and CEG-9 (9), were obtained, together with one known ganglioside, HLG-3 (7), from the lipid fraction of the chloroform/methanol extract of the sea cucumber Cucumaria echinata. The structures of the new gangliosides were determined on the basis of chemical and spectroscopic evidence to be 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-(2-->4)-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (6) and 1-O-[(N-glycolyl-D-neuraminosyl)-(2-->11)-(N-glycolyl-D-neuraminosyl)-(2-->4)-(N-acetyl-D-neuraminosyl)-(2-->6)-D-glucopyranosyl]-ceramide (8, 9). The ceramide moieties of each compound were composed of an homogeneous sphingosine or phytosphingosine base and heterogeneous 2-hydroxy or nonhydroxylated fatty acid units. These gangliosides showed neuritogenic activity toward the rat pheochromocytoma cell line PC-12 in the presence of nerve growth factor.
Assuntos
Cucumaria/química , Gangliosídeos , Holothuria/química , Animais , Configuração de Carboidratos , Sequência de Carboidratos , Sobrevivência Celular/efeitos dos fármacos , Gangliosídeos/síntese química , Gangliosídeos/química , Gangliosídeos/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/normas , Dados de Sequência Molecular , Fatores de Crescimento Neural/química , Neuritos/efeitos dos fármacos , Células PC12 , Ratos , Padrões de Referência , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Three new monosialo-gangliosides, CEG-3 (3), CEG-4 (4), and CEG-5 (5), were obtained, together with two known gangliosides, SJG-1 (1) and CG-1 (2), from the lipid fraction of the chloroform/methanol extract of the sea cucumber Cucumaria echinata. The structures of the new gangliosides were determined on the basis of chemical and spectroscopic evidence to be 1-O-[4-O-acetyl-alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (3) and 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (4, 5). The ceramide moieties of each compound were composed of heterogeneous sphingosine or phytosphingosine bases, and 2-hydroxy or nonhydroxylated fatty acid units. These gangliosides showed neuritogenic activity toward the rat pheochromocytoma cell line PC-12 in the presence of nerve growth factor.
Assuntos
Cucumaria/química , Gangliosídeos/química , Gangliosídeos/classificação , Holothuria/química , Animais , Clorofórmio/química , Gangliosídeos/análise , Gangliosídeos/isolamento & purificação , Gangliosídeos/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Metanol/química , Estrutura Molecular , Neuritos/efeitos dos fármacos , Células PC12 , Ratos , Solventes/químicaRESUMO
A ganglioside molecular species GP-3 (1) has been obtained from the water-soluble lipid fraction of the chloroform/methanol extract of the starfish Asterina pectinifera. The structure of the ganglioside has been determined on the basis of chemical and spectroscopic evidence. Compound 1 represents new ganglioside molecular species possessing two moles of sialic acids at the inner part of the sugar moiety. Partial hydrolysis by hot water and an enzymatic hydrolysis by means of endoglycoceramidase (EGCase) have proved useful for structure elucidation of the complex oligosaccharide moiety. Moreover, 1 exhibits neuritogenic activity toward the rat pheochromocytoma cell line, PC-12 cells, in the presence of nerve growth factor (NGF).
Assuntos
Gangliosídeos/química , Glicosídeos/química , Estrelas-do-Mar/fisiologia , Acetatos/química , Animais , Sequência de Carboidratos , Cromatografia em Camada Fina , Gangliosídeos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Glicosídeo Hidrolases/química , Glicosídeos/isolamento & purificação , Hidrólise , Espectroscopia de Ressonância Magnética , Metilação , Dados de Sequência Molecular , Fator de Crescimento Neural/farmacologia , Neuritos/efeitos dos fármacos , Células PC12 , Ratos , Espectrofotometria Infravermelho , Álcoois Açúcares/químicaRESUMO
A ganglioside molecular species, LLG-5 (1), has been obtained from the water soluble lipid fraction of the CHCl3/MeOH extract of the starfish Linckia laevigata. On the basis of chemical and spectroscopic findings, the structure of 1 has been elucidated. Negative ion FAB-MS provided important information both on the structure of the sugar moiety and on the molecular mass of the ganglioside. 1 is a new ganglioside molecular species possessing a 2-->11 linked linear-type trisialosyl moiety. Moreover, 1 exhibited neuritogenic activity in rat pheochromocytoma PC-12 cells in the presence of nerve growth factor.
Assuntos
Gangliosídeos/química , Gangliosídeos/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Neuritos/efeitos dos fármacos , Estrelas-do-Mar/química , Animais , Gangliosídeos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Glicosídeos/isolamento & purificação , Hidrólise , Espectroscopia de Ressonância Magnética , Metanol , Células PC12 , Ratos , Espectrofotometria Infravermelho , Álcoois Açúcares/químicaRESUMO
A glycosyl inositolphosphoceramide-type ganglioside, CJP4, was obtained from the polar lipid fraction of the chloroform/methanol extract of the feather star Comanthus japonica. The structure of this ganglioside has been determined on the basis of chemical and spectroscopic evidence to be 9-O-methyl-(N-glycolyl-alpha-D-neuraminosyl)-(2-->11)-9-O-methyl-(N-glycolyl-alpha-D-neuraminosyl)-(2-->11)-9-O-methyl-(N-glycolyl-alpha-D-neuraminosyl)-(2-->3)-inositolphosphoceramide, which contains C(16)-sphingosine and C(22:0)-, C(24:0)-fatty acid. This is the first report on the isolation and structural elucidation of a trisialo-glycosyl inositolphosphoceramide-type ganglioside. Moreover, CJP4 exhibited neuritogenic activity toward the rat pheochromocytoma PC12 cells in the presence of nerve growth factor.
Assuntos
Ceramidas/isolamento & purificação , Glicoesfingolipídeos/isolamento & purificação , Fatores de Crescimento Neural/isolamento & purificação , Estrelas-do-Mar/química , Animais , Linhagem Celular Tumoral , Ceramidas/química , Ceramidas/farmacologia , Glicoesfingolipídeos/química , Glicoesfingolipídeos/farmacologia , Estrutura Molecular , Fatores de Crescimento Neural/química , Fatores de Crescimento Neural/farmacologia , RatosRESUMO
A GD3-type ganglioside molecular species, LMG-4 (1), has been obtained from the polar lipid fraction of the chloroform/methanol extract of the starfish Luidia maculata. The structure of this ganglioside has been determined on the basis of chemical and spectroscopic evidence to be 1-O-[(N-acetyl-alpha-D-neuraminosyl)-(2-->8)-(N-acetyl-alpha-D-neuraminosyl)-(2-->3)-beta-D-galactopyranosyl-(1-->4)-beta-D-glucopyranosyl]-ceramide. The ceramide moiety was composed of heterogeneous 2-hydroxy fatty acid and phytosphingosine units. This is the first report on the isolation and structure elucidation of GD3-type ganglioside from echinoderms. Moreover, 1 exhibited neuritogenic activity toward the rat pheochromocytoma PC12 cells in the presence of nerve growth factor.
Assuntos
Gangliosídeos/isolamento & purificação , Neuritos/efeitos dos fármacos , Estrelas-do-Mar/química , Animais , Sequência de Carboidratos , Clorofórmio/química , Gangliosídeos/química , Gangliosídeos/farmacologia , Lipídeos/química , Metanol/química , Dados de Sequência Molecular , Neuritos/metabolismo , Células PC12 , Ratos , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
cis-Hinokiresinol (CHR) is a norlignan constituent from Anemarrhena asphodeloides BUNGE (Liliaceae), which shows hyaluronidase inhibitory activity. In the present studies, we have demonstrated that CHR selectively inhibited endothelial cell proliferation compared with cancer cells, and especially basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation. Furthermore, endothelial cell migration and tube formation, two important steps in the angiogenic process, were also inhibited by CHR. Moreover, CHR reduced the vessel growth induced by VEGF in the mouse corneal neovascularization model. These results suggest that CHR may prove useful for the development of a novel angiogenesis inhibitor.
Assuntos
Anemarrhena/química , Lignanas/química , Lignanas/farmacocinética , Neovascularização Patológica/prevenção & controle , Fenóis/farmacocinética , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/isolamento & purificação , Inibidores da Angiogênese/farmacocinética , Animais , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Córnea/irrigação sanguínea , Córnea/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Fator 2 de Crescimento de Fibroblastos/antagonistas & inibidores , Fator 2 de Crescimento de Fibroblastos/farmacologia , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/farmacocinética , Lignanas/efeitos adversos , Lignanas/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/etiologia , Farmacognosia/métodos , Fenóis/efeitos adversos , Fenóis/isolamento & purificação , Rizoma/química , Estereoisomerismo , Células Tumorais Cultivadas , Veias Umbilicais/citologia , Veias Umbilicais/efeitos dos fármacosRESUMO
An antiangiogenic purine analog, 1,3-dimethylisoguaninium (1), was isolated from the ethanol (EtOH) extract of the Okinawan sponge Amphimedon paraviridis. The structure was elucidated on the basis of its spectral properties and X-ray crystallographic analysis. Compound 1 exhibited specific inhibition of the basic fibroblast growth factor (bFGF)-induced proliferation of bovine aorta endothelial cells (BAECs). Moreover, compound 1 reduced the tube formation of BAECs in a time-dependent manner.
Assuntos
Inibidores da Angiogênese/isolamento & purificação , Células Endoteliais/efeitos dos fármacos , Guanina/análogos & derivados , Guanina/química , Poríferos/química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Bovinos , Divisão Celular/efeitos dos fármacos , Cristalografia por Raios X , Fatores de Crescimento de Fibroblastos/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
An ethanol (EtOH) extract of the soft coral (Sinularia sp.), collected in Okinawa, demonstrated a potent inhibitory effect on lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha (TNF-alpha) production by murine macrophage-like cells (RAW264.7). The activity-guided purification of the EtOH extract resulted in the isolation of two norditerpenes, norcembrenolide (1) and sinuleptolide (2). These structures were identified from the spectroscopic data. Norcembrenolide (1) and sinuleptolide (2) inhibited TNF-alpha production in a dose-dependent manner, and showed a more potent effect than prednisolone at the concentration of 33 microg/ml. They also exhibited an inhibitory effect on nitric oxide (NO) production not influenced by cytotoxicity.
Assuntos
Antozoários/química , Diterpenos/farmacologia , Hormônio do Crescimento Humano/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Interações Medicamentosas , Etanol/farmacologia , Glucocorticoides/farmacologia , Hormônio do Crescimento Humano/química , Hormônio do Crescimento Humano/classificação , Hormônio do Crescimento Humano/isolamento & purificação , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Prednisolona/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
Three ganglioside molecular species, SCG-1, SCG-2, and SCG-3, were obtained from the lipid fraction of the chloroform-methanol extract of the sea cucumber Stichopus chloronotus. On the basis of chemical and spectroscopic evidence, the structures of these gangliosides have been determined to be 1-O-[(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (SCG-1), 1-O-[8-O-sulfo(major)-(N-acetyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (SCG-2), and 1-O-[alpha-L-fucopyranosyl-(1-->11)-(N-glycolyl-alpha-D-neuraminosyl)-(2-->6)-beta-D-glucopyranosyl]-ceramide (SCG-3). The ceramide moieties were composed of heterogeneous long-chain base and fatty acid units. SCG-3 is the first type of ganglioside containing a fucopyranose in the sialosyl trisaccharide moiety. Moreover, these three gangliosides exhibited neuritogenic activity toward the rat pheochromocytoma PC12 cells in the presence of nerve growth factor.
Assuntos
Gangliosídeos/química , Neuritos/efeitos dos fármacos , Pepinos-do-Mar/química , Animais , Sequência de Carboidratos , Gangliosídeos/isolamento & purificação , Gangliosídeos/farmacologia , Dados de Sequência Molecular , Neuritos/fisiologia , Células PC12 , RatosRESUMO
[structure: see text] A novel diterpene, (-)-axinyssene, was isolated from the Japanese marine sponge Axinyssa sp. The structure of (-)-axinyssene was determined on the basis of spectroscopic and synthetic evidence to be 1-methyl-4-[(4E)-5',9'-dimethyl-1'-methylene-4',8'-decadienyl]-(4S)-cyclohexene. (-)- and (+)-axinyssene showed mild cytotoxicity against acute promyelocytic leukemia, HL-60 cells.
Assuntos
Citotoxinas/química , Diterpenos/química , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Divisão Celular/efeitos dos fármacos , Citotoxinas/isolamento & purificação , Diterpenos/isolamento & purificação , Células HL-60 , Humanos , Estrutura Molecular , Poríferos/química , Análise Espectral , EstereoisomerismoRESUMO
Costunolide (CT), a sesquiterpene lactone constituent isolated from Saussurea lappa (Compositae), exerted an antiangiogenic effect. CT selectively inhibited the endothelial cell proliferation induced by vascular endothelial growth factor (VEGF). Further, CT was also found to inhibit the VEGF-induced chemotaxis of human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner. From these results, we hypothesized that CT might inhibit angiogenesis by blocking the angiogenic factor signaling pathway. VEGF interacts with its cognate receptors, KDR/Flk-1 and Flt-1, and exerts its angiogenic effect. CT inhibited the autophosphorylation of KDR/Flk-1 without affecting that of Flt-1. Moreover, administration of CT reduced VEGF-induced neovascularization in a mouse corneal micropocket assay. These results suggest that CT may prove useful for the development of a novel angiogenesis inhibitor.
Assuntos
Inibidores da Angiogênese/farmacologia , Neovascularização da Córnea/prevenção & controle , Saussurea/química , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Células 3T3 , Inibidores da Angiogênese/isolamento & purificação , Animais , Divisão Celular/efeitos dos fármacos , Quimiotaxia , Neovascularização da Córnea/metabolismo , Relação Dose-Resposta a Droga , Fatores de Crescimento Endotelial/genética , Fatores de Crescimento Endotelial/metabolismo , Endotélio Vascular/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Linfocinas/genética , Linfocinas/metabolismo , Camundongos , Fosforilação , Sesquiterpenos/isolamento & purificação , Fator A de Crescimento do Endotélio Vascular , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio VascularRESUMO
A new antiangiogenic compound, bryoanthrathiophene (1), together with two known compounds, 5,7-dihydroxy-1-methoxycarbonyl-6-oxo-6H-anthra[1,9-bc]thiophene (2) and 1,8-dihydroxyanthraquinone (3), was isolated from the bryozoan Watersipora subtorquata (d'Orbigny, 1852) using bioassay-guided fractionation methods. Among them, bryoanthrathiophene (1) exhibited the most potent antiangiogenic activity on BAEC (bovine aorta endothelial cell) proliferation.