RESUMEN
The fungus Daedalea quercina (oak mazegill) was examined for its capability of producing antioxidative and anti-inflammatory compounds. Bioactivity guided fractionation of the extract from a mycelial culture led to the isolation of quercinol, which was identified as (-)-(2S)-2-hydroxymethyl-2-methyl-6-hydroxychromene 1 by NMR and X-ray analyses. The cryptic hydroquinone 1 shows a broad anti-inflammatory activity against cyclooxygenase 2 (COX-2), xanthine oxidase (XO), and horseradish peroxidase (HRP) at micromolar concentrations.
Asunto(s)
Antiinflamatorios/síntesis química , Antiinflamatorios/farmacología , Basidiomycota/metabolismo , Benzopiranos/química , Química Farmacéutica/métodos , Benzopiranos/síntesis química , Benzopiranos/farmacología , Cristalografía por Rayos X , Ciclooxigenasa 2/química , Inhibidores de la Ciclooxigenasa/farmacología , Diseño de Fármacos , Peroxidasa de Rábano Silvestre/antagonistas & inhibidores , Espectroscopía de Resonancia Magnética , Modelos Químicos , Conformación Molecular , Xantina Oxidasa/antagonistas & inhibidoresAsunto(s)
Antibacterianos/aislamiento & purificación , Basidiomycota/química , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Piperazinas/aislamiento & purificación , Animales , Antibacterianos/química , Antibacterianos/farmacología , División Celular/efectos de los fármacos , Línea Celular , Fibroblastos/efectos de los fármacos , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Células HeLa , Compuestos Heterocíclicos de 4 o más Anillos/química , Humanos , Células K562/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Ratones , Pruebas de Sensibilidad Microbiana , Piperazinas/química , Piperazinas/farmacología , Espectrometría de Masa por Ionización de ElectrosprayAsunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Lípidos/química , Lípidos/farmacología , Hongos Mitospóricos/química , Oligopéptidos/química , Oligopéptidos/farmacología , Animales , Antibacterianos/aislamiento & purificación , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/aislamiento & purificación , Antibióticos Antineoplásicos/farmacología , División Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Fibroblastos/efectos de los fármacos , Hongos/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Células HeLa/efectos de los fármacos , Humanos , Hidrólisis , Lípidos/aislamiento & purificación , Espectrometría de Masas/métodos , Ratones , Pruebas de Sensibilidad Microbiana , Hongos Mitospóricos/metabolismo , Estructura Molecular , Oligopéptidos/aislamiento & purificaciónRESUMEN
The conformation of the 19-residue peptaibol chrysospermin C in methanol has been investigated by NMR spectroscopy using selective 15N and 13C labeling of the alpha-aminoisobutyric acid (Aib) residues. Complete 1H and 13C sequential assignments, including stereospecific assignments for the heavily overlapped resonances from the two Cbeta methyl groups of the eight Aib residues, are reported for a peptaibol for the first time. An Aib residue followed by a Pro is an exception to previous suggestions regarding stereospecific assignment of the two Cbeta methyl groups of Aib residues. Local nuclear Overhauser effects and 3J(HNC') and 3J(HNCbeta) scalar couplings indicate that the phi angles of the Aib residues are restricted sterically to local conformations consistent with right-handed helices. Despite these constraints on the eight Aib residues, the NMR data for chrysospermin C in methanol are generally most consistent with an ensemble of transient conformations, including backbone conformations inconsistent with helical structures. Initial NMR measurements for chrysospermin C bound to micelles suggest structural and dynamic differences relative to alamethicin bound to micelles which may be related to differences in gating voltages for formation of ion channels.
Asunto(s)
Antibacterianos/química , Péptidos , Secuencia de Aminoácidos , Antifúngicos/química , Espectroscopía de Resonancia Magnética , Metanol/farmacología , Conformación Molecular , Datos de Secuencia Molecular , Peptaiboles , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacología , Estructura Secundaria de ProteínaRESUMEN
A novel natural niphimycin analog, N'-methylniphimycin was isolated from the culture broth of the Streptomyces spec. 57-13. The chemical constitution was elucidated from the physico-chemical properties, NMR techniques and mass spectrometry to be a 36-membered macrolide related to azalomycin F5a, shurimycin B and RS-22C. N'-methylniphimycin displayed moderate activity against some yeasts and filamentous fungi.
Asunto(s)
Antifúngicos/química , Streptomyces/química , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Cromatografía Líquida de Alta Presión , Hongos/efectos de los fármacos , Guanidinas/química , Guanidinas/aislamiento & purificación , Guanidinas/farmacología , Espectrometría de Masas , Streptomyces/crecimiento & desarrollo , Levaduras/efectos de los fármacosRESUMEN
Ampullosporin (I; Ac-Trp-Ala-Aib-Aib-Leu-Aib-Gln-Aib-Aib-Aib-Gln-Leu-Aib-Gln-Leuol) was isolated from the mycelium of Sepedonium ampullosporum as a new 15-membered peptaibol-type antibiotic. The structure was determined by mass spectrometric and two-dimensional NMR experiments. Ampullosporin displays narrow-spectrum antibacterial and antifungal activity, induces pigment formation by Phoma destructiva, causes hypothermia and decreased spontaneous locomotor activity in mice in dosages > 1 mg/kg.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Péptidos , Animales , Antibacterianos/química , Antifúngicos/química , Cromatografía Líquida de Alta Presión , Femenino , Masculino , Ratones , Pruebas de Sensibilidad Microbiana , Hongos Mitospóricos , Estructura Molecular , PeptaibolesAsunto(s)
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/aislamiento & purificación , Animales , Antibióticos Antineoplásicos/farmacología , Benzo(a)Antracenos/química , Benzo(a)Antracenos/aislamiento & purificación , Benzo(a)Antracenos/farmacología , Fermentación , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Streptomyces , Células Tumorales CultivadasRESUMEN
Lipohexin was isolated as a novel lipohexapeptide (I) (C39H68N6O9) from three fungal strains, Moeszia lindtneri HKI-0054, Paecilomyces sp. HKI-0055 and Paecilomyces sp. HKI-0096. The structure was elucidated by detailed mass spectrometric and NMR experiments. The proline-containing peptide displays moderate antibacterial activity against Bacillus subtilis ATCC 6633 and inhibits competitively the prolyl endopeptidase from human placenta.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Lipoproteínas/aislamiento & purificación , Lipoproteínas/farmacología , Péptidos , Serina Endopeptidasas/metabolismo , Inhibidores de Serina Proteinasa/aislamiento & purificación , Inhibidores de Serina Proteinasa/farmacología , Antibacterianos/química , Bacillus subtilis/efectos de los fármacos , Humanos , Lipoproteínas/química , Pruebas de Sensibilidad Microbiana , Hongos Mitospóricos/metabolismo , Estructura Molecular , Paecilomyces/metabolismo , Prolil Oligopeptidasas , Inhibidores de Serina Proteinasa/químicaRESUMEN
Radii of ion channels formed in the lipid bilayer by 4 homologs of the alamethicin-like antibiotic, chrysospermin, were determined using hydrophilic nonelectrolytes. It is shown that the replacement of isovaline amino acid at position 15 of the polypeptide chain by alpha-aminoisobutyric acid results in the decrease in the channel effective radius from 1.2 +/- 0.15 to 0.94 +/- 0.1 nm and a respective 2.5-fold decrease in channel conductance.
Asunto(s)
Antibacterianos , Antifúngicos , Canales Iónicos/química , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Antifúngicos/química , Péptidos Catiónicos Antimicrobianos , Conductividad Eléctrica , Canales Iónicos/ultraestructura , Membrana Dobles de Lípidos/química , Datos de Secuencia Molecular , Peptaiboles , Péptidos/químicaRESUMEN
Four new members of peptaibol antibiotics, designated as chrysospermins A, B, C, and D, were isolated from the mycelium of Apiocrea chrysosperma Ap101 by solvent extraction, silica gel chromatography and preparative recycling HPLC. Their structures as new nonadecapeptides were settled by detailed spectroscopic analysis and chemical degradation experiments. The chrysospermins display antibacterial and antifungal activity, and induce pigment formation by the fungus Phoma destructiva.
Asunto(s)
Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Secuencia de Aminoácidos , Aminoácidos/análisis , Antibacterianos/farmacología , Antifúngicos/farmacología , Péptidos Catiónicos Antimicrobianos , Ascomicetos , Fermentación , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Peptaiboles , Péptidos/química , Péptidos/aislamiento & purificación , Péptidos/farmacología , Espectrometría de Masa Bombardeada por Átomos VelocesRESUMEN
The four homologous chrysospermins (Ia-d) are new 19 amino acid peptaibols which form cation selective ion channels in artificial lipid bilayer membranes. Conductance of channels formed by chrysospermins B (Ib) and D (Id) was twice as high (640 pS in 100 mM KCl) as found with chrysospermins A (Ia) and C (Ic). Single channel current traces were recorded for each of the four peptides even at very low (even zero) membrane voltages suggesting that non-gated channels are formed.
Asunto(s)
Antibacterianos/farmacología , Canales Iónicos/efectos de los fármacos , Membranas Artificiales , Oligopéptidos/farmacología , Secuencia de Aminoácidos , Aminoácidos/química , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Hongos/química , Datos de Secuencia MolecularRESUMEN
Aurantimycins A (1), B (2) and C (3) were isolated from the mycelium of Streptomyces aurantiacus JA 4570 as new representatives of the azinothricin group of hexadepsipeptide antibiotics. Their structures were settled by X-ray diffraction analysis of crystalline aurantimycin A (1), high field homo- and heteronuclear 2D NMR experiments, high-resolution mass spectrometry and amino acid analysis. Aurantimycins are characterized by a new side chain containing fourteen carbon atoms. They display strong activity against Gram-positive bacteria and cytotoxic effects against L-929 mouse fibroblast cells.
Asunto(s)
Antibacterianos/biosíntesis , Péptidos , Streptomyces/metabolismo , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Línea Celular , Citotoxinas/biosíntesis , Citotoxinas/química , Citotoxinas/aislamiento & purificación , Citotoxinas/farmacología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Espectrometría de Masa Bombardeada por Átomos Veloces , Difracción de Rayos XRESUMEN
During the last decade new anthracycline-type structures with potential usefulness in cancer treatment have been supplied both by new microbial strains and by bioconversions of precursor molecules employing cells or enzymes. We highlight recent advances in bioconversion of anthracycline structures with the main focus on late transformations such as are carried out by oxidoreductases.
RESUMEN
The enzymatic interconversion of the aclacinomycins A (I), Y (II), and B (III) by Streptomyces spec. AM 33352/S 182 producing these aklavinone glycosides was investigated. The enzymes converting I to II and III, as well as vice versa, are located within different compartments separated by the cytoplasmic membrane. Aclacinomycin A (I) is biotransformed to II and III by the cell-free mycelium extract while the entire mycelium carries out the same type of conversion towards the opposite direction. Changes of enzyme activity are correlated to alterations in the ratio of aklavinone glycosides throughout the fermentation. A hypothesis is developed concerning the role of compartmentized oxidoreductase(s) in the passive flux of I from inside the cells to outside.
Asunto(s)
Aclarubicina/análogos & derivados , Streptomyces/enzimología , Aclarubicina/biosíntesis , Aclarubicina/metabolismo , Centrifugación por Gradiente de Densidad , Fenómenos Químicos , Química , Fermentación , Streptomyces/metabolismoRESUMEN
The reductive cleavage of the aclacinomycins A (I), Y (II), and B (III) by intact mycelia or subcellular fractions of the producer strain S. spec. AM 33352/F43 is suppressed in the presence of uncouplers, complex-forming agents, detergents, and some metal anions such as chromate. Increased concentration of the latter in complete cultures caused rearrangement of I to III.
RESUMEN
In a continuing search for potent antineoplastic compounds in indigenous plants, a water extract of Physalis alkekengi L. var. franchetii Mast. fruits was shown to have reproducible antineoplastic activity against Ehrlich ascites carcinoma in mice. Systematic fractionation of the extract led to the isolation of citric acid as the major active principle.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Animales , Antineoplásicos Fitogénicos/análisis , Antineoplásicos Fitogénicos/aislamiento & purificación , Carcinoma de Ehrlich/tratamiento farmacológico , Cromatografía por Intercambio Iónico , Citratos/análisis , Ácido Cítrico , Femenino , Masculino , Ratones , Ratones Endogámicos DBARESUMEN
By using a strain of Streptomyces willmorii, daunorubicin (daunomycin) was stereoselectively converted into N-acetyl-13(S)-dihydrodaunomycin and bisanhydro-13-dihydrodaunomycinone. The absolute stereochemistry of the new chiral center in N-acetyl-13(S)-dihydrodaunomycin was established by means of nuclear Overhauser effect measured in the 9,13-O-isopropylidene derivative.
Asunto(s)
Daunorrubicina/análogos & derivados , Daunorrubicina/metabolismo , Naftacenos/metabolismo , Streptomyces/metabolismo , Fermentación , Conformación MolecularRESUMEN
693 kinds of indigenous plants randomly selected were screened for their antimicrobial activities against 23 different test organisms (Gram-positive, Gram-negative bacteria, yeast and fungi). The results of the testing showed that 250 (36%) kinds of the plants belonging to 72 families exhibited some level of antimicrobial action in vitro. Moreover, a microbiological prescreening program was employed in search of presumed cancerostatic plant products in crude extracts. These microbial tests based on agar diffusion techniques consist of prophage induction test and BIP test (bacteria inhibition-induction-phage inhibition). All active components selected by these microbial models are potential inhibitors of nucleic acid metabolism. A wide variety of plants was demonstrated to exhibit interesting activities in these screening systems. The bioactivity is uniformly distributed in various order. The screening results are briefly discussed.