RESUMO
A new member of the angucycline family, vineomycin C (3), together with four known metabolites saquayamycin A1 (1), A-7884 (2), rabelomycin (5) and xanthomegnin (6) were isolated from microbial extracts. The structures were determined by 1D and 2D NMR techniques and chemical degradation. Compounds 1-3 and 5 were isolated from a fermentation of Streptomyces sp., while 6 was isolated from a fungal fermentation extract. All five compounds have shown potent inhibitory activity in the inducible nitric oxide synthase (iNOS) assay.
Assuntos
Antraquinonas/química , Inibidores Enzimáticos/química , Óxido Nítrico Sintase/antagonistas & inibidores , Streptomyces/química , Animais , Antraquinonas/isolamento & purificação , Antraquinonas/farmacologia , Linhagem Celular , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II , Análise EspectralRESUMO
Two inhibitors of CD45 tyrosine phosphatase, dihydrocarolic acid (1) and penitricin D (2), were isolated from a fermentation broth of the fungus Aspergillus niger and purified by HSCCC (high speed countercurrent chromatography) followed by HPLC. The structures were determined by NMR. The inhibitory activities of both compounds were specific to tyrosine phosphatases.
Assuntos
Aspergillus niger/química , Ciclopropanos/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Furanos/isolamento & purificação , Furanos/farmacologia , Antígenos Comuns de Leucócito/metabolismo , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Aspergillus niger/metabolismo , Divisão Celular/efeitos dos fármacos , Inibidores Enzimáticos/química , Fator de Crescimento Epidérmico/farmacologia , Fermentação , Fibroblastos/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Antígenos Comuns de Leucócito/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
Five new asterriquinone analogs (2-4, 6, 7), together with previously identified neoasterriquinone (1) and isoasterriquinone (5), were isolated from a fermentation broth of the fungus Aspergillus candidus and purified by HSCCC (high speed counter current chromatography) followed by HPLC. The structures were determined by 1D and 2D NMR and MS/MS techniques. All seven showed inhibitory activity against the binding of a recombinant protein containing the SH2 protein domain of Grb-2 to the tyrosine phosphorylated form of the EGF receptor tyrosine kinase. Some of these asterriquinones exhibited specific inhibition of Grb-2 binding compared to Grb-7 and PLC-gamma.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Antibióticos Antineoplásicos/farmacologia , Aspergillus/metabolismo , Proteínas de Transporte/antagonistas & inibidores , Receptores ErbB/metabolismo , Antibióticos Antineoplásicos/isolamento & purificação , Antibióticos Antineoplásicos/metabolismo , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Ensaio de Imunoadsorção Enzimática , Fermentação , Glutationa Transferase/metabolismo , Humanos , Immunoblotting , Indóis/isolamento & purificação , Indóis/metabolismo , Indóis/farmacologia , Espectroscopia de Ressonância Magnética , Fosforilação , Ligação Proteica , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Ultravioleta , Domínios de Homologia de srcAssuntos
Ascomicetos/química , Inibidores Enzimáticos/farmacologia , Lactamas/farmacologia , Antígenos Comuns de Leucócito/efeitos dos fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Lactamas/química , Lactamas/isolamento & purificação , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Proteínas Recombinantes/antagonistas & inibidoresAssuntos
Cefalosporinas/isolamento & purificação , Transferases Intramoleculares , Isomerases/metabolismo , Proteínas de Ligação às Penicilinas , Penicillium chrysogenum/metabolismo , Cefalosporinas/biossíntese , Cefalosporinas/química , Fenômenos Químicos , Físico-Química , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Penicillium chrysogenum/enzimologia , Espectrofotometria UltravioletaRESUMO
Studies on the alkaloidal constituents of the leaves of Ervatamia coronaria Stapf and Alstonia scholaris have resulted in the isolation of (20 S)-19,20-dihydrocondylocarpine which has not been previously reported from these plants. The stereochemistry at C-20 was established with the help of n. O. e. difference measurements. (13)C-NMR assignments have been made by polarisation transfer techniques.
RESUMO
The marine sponge Lendenfeldia frondosa, collected from the Solomon Islands, has yielded homoscalarane sesterterpenes. Two new metabolites, epihomoscalaralactone IIA [5] and homoscalarate II [10], were accompanied by two known metabolites, homoscalaralactone IIA [1] and homoscalaralactone IIB [7]. These structures were established by analysis of 2D nmr data, trends in 13C-nmr shifts, and comparison of experimental with molecular-mechanics-calculated nmr J's. Each of the alcohols 1, 2, and 3 was converted to its corresponding acetate, 2, 6, and 8, respectively. Compound 6 exhibited moderate anti-inflammatory activity.
Assuntos
Poríferos/química , Terpenos/química , Animais , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Relação Estrutura-Atividade , Terpenos/isolamento & purificaçãoRESUMO
The study of the anthelmintic terpenoid components from the Fiji sponge Axinyssa fenestratus (senior synonym of Leucophloeus fenestratus) and two Thailand sponges, Acanthella cavernosa and Topsentia sp., has yielded several new nitrogen-containing sesqui- and diterpenes of known carbon skeletons. Amorphane sesquiterpenes from A. fenestratus included (1R, 6S, 7S, 10S)-10-isothiocyanato-4-amorphene [(+)-1] and new metabolites (1R*, 4S*, 6R*, 7S*)-4-isothiocyanato-9-amorphene [2], 10-isothiocyanato-4,6-amorphadiene [3], and (4S*, 10S*)-10-isothiocyanato-5-amorphen-4-ol [4]. The amorphene (+)-1 of this study may be antipodal to (-)-1 previously isolated from a Hawaiian sponge. A similar relationship may exist at C-1, C-6, C-7 between (+)-2 of this study and (-)-11 isolated from a Palauian sponge. Another known sesquiterpene, axisonitrile 3 [5] was obtained from Topsentia sp. The diterpenes obtained from A. cavernosa included known kalihinols X [6] and Y [8] and new kalihinols J [7] and I [9]. Those terpenoids with potent antiparasite activity include 1, 2, 3-5, and 7-9.
Assuntos
Anti-Helmínticos/isolamento & purificação , Poríferos/análise , Terpenos/farmacologia , Animais , Anti-Helmínticos/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Nitrogênio/química , Terpenos/química , Terpenos/isolamento & purificaçãoRESUMO
During the course of screening microbial broth extracts in various high through-put bioassays (eg receptor binding or enzyme inhibition), several actinomycete cultures were discovered to produce active metabolites. The natural products elaiophylin and/or geldanamycin are produced by several Streptomyces violaceusniger strains, and the bioactivity of the extracts from these cultures was frequently associated with the fractions containing these metabolites. CPC coupled to a photodiode array detector and LC-MS techniques were applied to these broth extracts to ascertain rapidly when these natural products were present. These methodologies allowed us to identify the metabolites quickly in the crude extract, and the application demonstrated further the utility of CPC-photodiode array detection and LC-MS as powerful, initial analytical tools in analyses of the complex metabolite profiles produced by microorganisms.
Assuntos
Antibacterianos/isolamento & purificação , Cromatografia , Cromatografia Gasosa-Espectrometria de Massas , Macrolídeos , Quinonas/isolamento & purificação , Streptomyces/metabolismo , Antibacterianos/metabolismo , Benzoquinonas , Cromatografia/métodos , Fermentação , Lactamas Macrocíclicas , Quinonas/metabolismo , Fatores de TempoRESUMO
The marine polyketide natural product, halenaquinone, was shown to be an irreversible inhibitor of pp60v-src, the oncogenic protein tyrosine kinase encoded by the Rous sarcoma virus. This compound had an IC50 of approximately 1.5 microM against pp60v-src and also inhibited the ligand-stimulated kinase activity of the human epidermal growth factor receptor with an IC50 of approximately 19 microM. Halenaquinone blocked the proliferation of a number of cultured cell lines, including several transformed by oncogenic protein tyrosine kinases. Halenaquinol, xestoquinone, halenaquinol sulfate, and several simple synthetic quinone analogs were also shown to inhibit pp60v-src.
Assuntos
Proteína Oncogênica pp60(v-src)/antagonistas & inibidores , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinonas/farmacologia , Animais , Vírus do Sarcoma Aviário/enzimologia , Células CHO , Carcinoma de Células Escamosas , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Cricetinae , Receptores ErbB/antagonistas & inibidores , Humanos , Cinética , Estrutura Molecular , Poríferos , Quinonas/química , Relação Estrutura-AtividadeRESUMO
A new diterpenoid lactone, angasiol acetate [1], has been isolated from the sea hare Aplysia juliana collected from the Karachi coastline of the Arabian ocean. The structure, including the absolute configuration of 1, was determined by single-crystal X-ray diffraction and spectroscopic techniques.