RESUMO
Activity-guided fractionations of the tunicate Pseudodistoma antinboja yielded four new compounds of the cadiolide class (cadiolides J-M, 1, 3-5) along with a known one (cadiolide H, 2). The structures were defined by spectroscopic methods including X-ray crystallographic analysis. These compounds were evaluated for their antibacterial activity and exhibited potent antibacterial activity against all of the drug resistant strains tested with MICs comparable to those of marketed drugs such as vancomycin and linezolid.
Assuntos
4-Butirolactona/análogos & derivados , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Urocordados/química , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Estrutura Molecular , República da Coreia , Relação Estrutura-AtividadeRESUMO
A new inhibitor, acredinone C (1), of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation was isolated from the culture broth of the fungus Acremonium sp. (F9A015) along with acredinones A (2) and B (3). The structure of acredinone C (1), which incorporates benzophenone and xanthone moieties, was established by the analyses of combined spectroscopic data including 1D and 2D NMR and MS. All of the acredinones studied efficiently inhibited the RANKL-induced formation of TRAP(+)-MNCs in a dose-dependent manner without any cytotoxicity up to 10 µM. Acredinone A showed dual activity in both osteoclast and osteoblast differentiation in vitro and good efficacy in an animal disease model of bone formation.
Assuntos
Acremonium/química , Benzofenonas/farmacologia , Animais , Benzofenonas/química , Diferenciação Celular , Modelos Animais de Doenças , Camundongos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ligante RANK/antagonistas & inibidoresRESUMO
Two new benzophenones, acredinones A (1) and B (2), were isolated from a marine-sponge-associated Acremonium sp. fungus. Their chemical structures were elucidated on the interpretation of spectroscopic data. The structure of 1 was confirmed by palladium-catalyzed hydrogenation, followed by spectroscopic data analysis. Acredinones A (1) and B (2) inhibited the outward K(+) currents of the insulin secreting cell line INS-1 with IC50 values of 0.59 and 1.0 µM, respectively.
Assuntos
Acremonium/química , Benzofenonas/isolamento & purificação , Benzofenonas/farmacologia , Poríferos/microbiologia , Bloqueadores dos Canais de Potássio/isolamento & purificação , Bloqueadores dos Canais de Potássio/farmacologia , Animais , Benzofenonas/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Concentração Inibidora 50 , Insulina/metabolismo , Secreção de Insulina , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Bloqueadores dos Canais de Potássio/químicaRESUMO
Chemical investigation of a Korean marine sponge, Monanchora sp., led to the isolation of three new steroids (1-3). Compounds 1 and 2, designated as monanchosterols A and B, respectively, represent the first examples of steroids possessing the bicyclo[4.3.1] A/B ring system from a natural source. Compounds 1-3 were investigated for their anti-inflammatory activity by evaluating their inhibitory effects on the mRNA expression of IL-6, TNF-α, and COX-2 in the LPS-stimulated murine RAW264.7 macrophage cells. Compounds 2 and 3 exhibited significant inhibitory effects on the mRNA expression of IL-6 without notable cytotoxicity to the cells in a dose-dependent manner.
Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Compostos Bicíclicos com Pontes/isolamento & purificação , Compostos Bicíclicos com Pontes/farmacologia , Poríferos/química , Esteroides/isolamento & purificação , Animais , Anti-Inflamatórios/química , Compostos Bicíclicos com Pontes/química , Ciclo-Oxigenase 2/metabolismo , Relação Dose-Resposta a Droga , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Biologia Marinha , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Ressonância Magnética Nuclear Biomolecular , República da Coreia , Esteroides/química , Esteroides/farmacologia , Fator de Necrose Tumoral alfa/efeitos dos fármacosRESUMO
Three new sterols, 5α,8α-epidioxy-24-norcholesta-6,9(11),22-trien-3ß-ol (1), 5α,8α-epidioxy-cholesta-6,9(11),24-trien-3ß-ol (2), and 5α,8α-epidioxy-cholesta-6,23-dien-3ß,25-diol (3), with four known sterols (4-7) were isolated from a marine sponge Monanchora sp. Their chemical structures were elucidated by extensive spectroscopic analysis. Compounds 1 and 3-7 showed moderate cytotoxicity against several human carcinoma cell lines including renal (A-498), pancreatic (PANC-1 and MIA PaCa-2), and colorectal (HCT 116) cancer cell lines.
Assuntos
Colestadienóis/isolamento & purificação , Colestadienóis/farmacologia , Colestenos/isolamento & purificação , Colestenos/farmacologia , Noresteroides/isolamento & purificação , Noresteroides/farmacologia , Poríferos/química , Esteróis/isolamento & purificação , Esteróis/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Esteróis/toxicidadeRESUMO
Three new sesterterpenoids, phorbaketals L-N (1-3), were isolated from a marine sponge of the genus Phorbas and their complete structures were elucidated via analysis of HRFABMS and NMR spectroscopic data. Phorbaketal N (3) showed potent cytotoxicity against human pancreas cancer cells (IC50=11.4 µM).
Assuntos
Neoplasias Pancreáticas/patologia , Poríferos/química , Sesterterpenos/toxicidade , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
Anmindenols A (1) and B (2), inhibitors of inducible nitric oxide synthase (iNOS), were isolated from a marine-derived bacterium Streptomyces sp. Their chemical structures were elucidated by interpreting various spectroscopic data, including IR, MS, and NMR. Anmindenols A and B are sesquiterpenoids possessing an indene moiety with five- and six-membered rings derived from isoprenyl units. The absolute configuration of C-4 in anmindenol B was determined by electronic circular dichroism (ECD) of a dimolybdenum complex. Anmindenols A (1) and B (2) inhibited nitric oxide production in stimulated RAW 264.7 macrophage cells with IC50 values of 23 and 19 µM, respectively.
Assuntos
Indenos/isolamento & purificação , Indenos/farmacologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Streptomyces/química , Animais , Indenos/química , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Biologia Marinha , Camundongos , Estrutura Molecular , NF-kappa B/metabolismo , Óxido Nítrico/biossíntese , Ressonância Magnética Nuclear Biomolecular , Sesquiterpenos/químicaRESUMO
A new inhibitor, placotylene A (1), of the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation, and a regioisomer of placotylene A, placotylene B (2), were isolated from a Korean marine sponge Placospongia sp. The chemical structures of placotylenes A and B were elucidated on the basis of 1D and 2D NMR, along with MS spectral analysis and revealed as an iodinated polyacetylene class of natural products. Placotylene A (1) displayed inhibitory activity against RANKL-induced osteoclast differentiation at 10 µM while placotylene B (2) did not show any significant activity up to 100 µM, respectively.
Assuntos
Di-Inos/farmacologia , Álcoois Graxos/farmacologia , Osteoclastos/efeitos dos fármacos , Poríferos/química , Animais , Diferenciação Celular/efeitos dos fármacos , Di-Inos/química , Di-Inos/isolamento & purificação , Relação Dose-Resposta a Droga , Álcoois Graxos/química , Álcoois Graxos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR , Osteoclastos/metabolismo , Ligante RANK/metabolismo , República da Coreia , EstereoisomerismoRESUMO
Three novel scalarane sesterterpenes were isolated from a Korean marine sponge, Psammocinia sp., along with four known derivatives. Their structures were elucidated on the basis of NMR, MS and IR spectroscopic data. The three new compounds are 12-deacetoxy-23-hydroxyscalaradial (1), 12-dehydroxy-23-hydroxyhyrtiolide (2) and 12-O-acetyl-16-deacetoxy-23-acetoxyscalarafuran (3), respectively, and the four known compounds are 12-deacetoxy-23-hydroxyheteronemin (4), 12-deacetoxy-23-acetoxy-19-O-acetylscalarin (5), 12-deacetoxy-23-O-acetoxyheteronemin (6) and 12-deacetoxyscalaradial (7). They exhibited cytotoxicity against intractable human cancer cell lines A498, ACHN, MIA-paca and PANC-1, with an IC50 range of 0.4-48 µM.