RESUMO
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.
Assuntos
Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Basidiomycota/metabolismo , Benzopiranos/química , Química Farmacêutica/métodos , Benzopiranos/síntese química , Benzopiranos/farmacologia , Cristalografia por Raios X , Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase/farmacologia , Desenho de Fármacos , Peroxidase do Rábano Silvestre/antagonistas & inibidores , Espectroscopia de Ressonância Magnética , Modelos Químicos , Conformação Molecular , Xantina Oxidase/antagonistas & inibidoresAssuntos
Antibacterianos/isolamento & purificação , Basidiomycota/química , Compostos Heterocíclicos de 4 ou mais Anéis/isolamento & purificação , Piperazinas/isolamento & purificação , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Fibroblastos/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa , Compostos Heterocíclicos de 4 ou mais Anéis/química , Humanos , Células K562/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Testes de Sensibilidade Microbiana , Piperazinas/química , Piperazinas/farmacologia , Espectrometria de Massas por Ionização por ElectrosprayAssuntos
Antibacterianos/química , Antibacterianos/farmacologia , Lipídeos/química , Lipídeos/farmacologia , Fungos Mitospóricos/química , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Animais , Antibacterianos/isolamento & purificação , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/isolamento & purificação , Antibióticos Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Fibroblastos/efeitos dos fármacos , Fungos/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Células HeLa/efeitos dos fármacos , Humanos , Hidrólise , Lipídeos/isolamento & purificação , Espectrometria de Massas/métodos , Camundongos , Testes de Sensibilidade Microbiana , Fungos Mitospóricos/metabolismo , Estrutura Molecular , Oligopeptídeos/isolamento & purificaçãoRESUMO
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.
Assuntos
Antibacterianos/química , Peptídeos , Sequência de Aminoácidos , Antifúngicos/química , Espectroscopia de Ressonância Magnética , Metanol/farmacologia , Conformação Molecular , Dados de Sequência Molecular , Peptaibols , Fosforilcolina/análogos & derivados , Fosforilcolina/farmacologia , Estrutura Secundária de ProteínaRESUMO
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.
Assuntos
Antifúngicos/química , Streptomyces/química , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Cromatografia Líquida de Alta Pressão , Fungos/efeitos dos fármacos , Guanidinas/química , Guanidinas/isolamento & purificação , Guanidinas/farmacologia , Espectrometria de Massas , Streptomyces/crescimento & desenvolvimento , Leveduras/efeitos dos fármacosRESUMO
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.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antifúngicos/isolamento & purificação , Antifúngicos/farmacologia , Peptídeos , Animais , Antibacterianos/química , Antifúngicos/química , Cromatografia Líquida de Alta Pressão , Feminino , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Fungos Mitospóricos , Estrutura Molecular , PeptaibolsAssuntos
Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/isolamento & purificação , Animais , Antibióticos Antineoplásicos/farmacologia , Benzo(a)Antracenos/química , Benzo(a)Antracenos/isolamento & purificação , Benzo(a)Antracenos/farmacologia , Fermentação , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Streptomyces , Células Tumorais CultivadasRESUMO
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.
Assuntos
Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Lipoproteínas/isolamento & purificação , Lipoproteínas/farmacologia , Peptídeos , Serina Endopeptidases/metabolismo , Inibidores de Serina Proteinase/isolamento & purificação , Inibidores de Serina Proteinase/farmacologia , Antibacterianos/química , Bacillus subtilis/efeitos dos fármacos , Humanos , Lipoproteínas/química , Testes de Sensibilidade Microbiana , Fungos Mitospóricos/metabolismo , Estrutura Molecular , Paecilomyces/metabolismo , Prolil Oligopeptidases , Inibidores de Serina Proteinase/químicaRESUMO
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.
Assuntos
Antibacterianos , Antifúngicos , Canais Iônicos/química , Sequência de Aminoácidos , Substituição de Aminoácidos , Antifúngicos/química , Peptídeos Catiônicos Antimicrobianos , Condutividade Elétrica , Canais Iônicos/ultraestrutura , Bicamadas Lipídicas/química , Dados de Sequência Molecular , Peptaibols , Peptídeos/químicaRESUMO
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.
Assuntos
Antibacterianos/química , Antibacterianos/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Sequência de Aminoácidos , Aminoácidos/análise , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Peptídeos Catiônicos Antimicrobianos , Ascomicetos , Fermentação , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Peptaibols , Peptídeos/química , Peptídeos/isolamento & purificação , Peptídeos/farmacologia , Espectrometria de Massas de Bombardeamento Rápido de ÁtomosRESUMO
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.
Assuntos
Antibacterianos/farmacologia , Canais Iônicos/efeitos dos fármacos , Membranas Artificiais , Oligopeptídeos/farmacologia , Sequência de Aminoácidos , Aminoácidos/química , Antibacterianos/química , Antibacterianos/isolamento & purificação , Fungos/química , Dados de Sequência MolecularRESUMO
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.
Assuntos
Antibacterianos/biossíntese , Peptídeos , Streptomyces/metabolismo , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Linhagem Celular , Citotoxinas/biossíntese , Citotoxinas/química , Citotoxinas/isolamento & purificação , Citotoxinas/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Difração de Raios XRESUMO
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.
RESUMO
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.
Assuntos
Aclarubicina/análogos & derivados , Streptomyces/enzimologia , Aclarubicina/biossíntese , Aclarubicina/metabolismo , Centrifugação com Gradiente de Concentração , Fenômenos Químicos , Química , Fermentação , Streptomyces/metabolismoRESUMO
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.
RESUMO
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.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antineoplásicos Fitogênicos/análise , Antineoplásicos Fitogênicos/isolamento & purificação , Carcinoma de Ehrlich/tratamento farmacológico , Cromatografia por Troca Iônica , Citratos/análise , Ácido Cítrico , Feminino , Masculino , Camundongos , Camundongos Endogâmicos DBARESUMO
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.
Assuntos
Daunorrubicina/análogos & derivados , Daunorrubicina/metabolismo , Naftacenos/metabolismo , Streptomyces/metabolismo , Fermentação , Conformação MolecularRESUMO
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.