RESUMEN
Naturally occurring carbapenem antibiotics having a double bond in the side chain, when refluxed in chloroform containing quarternary alkylammonium halides, were converted into Z isomers in high yields. The mechanism of this new equilibration involves intramolecular proton transfer from the carboxylic acid to the carbon alpha to the sulfur atom in the side chain as shown by deuterium-labeling experiments. Some Z isomers showed stronger protective effects in mice infected by Escherichia coli O-111 and more potent synergistic activities with cefotiam in mice infected by Proteus vulgaris GN4815 than did the naturally occurring E isomers. The decomposition rates of the Z isomers in mouse kidney homogenates were about 3-fold slower than those of the E isomers.
Asunto(s)
Antibacterianos , Tienamicinas , Animales , Antibacterianos/síntesis química , Escherichia coli/efectos de los fármacos , Isomerismo , Ratones , Proteus vulgaris/efectos de los fármacos , Relación Estructura-Actividad , Tienamicinas/farmacologíaRESUMEN
Naturally occurring carbapenem antibiotics having a double bond in the side chain, when refluxed in chloroform containing quarternary alkylammonium halides, were converted into Z isomers in high yields. The mechanism of this new equilibration involves intramolecular proton transfer from the carboxylic acid to the carbon alpha to the sulfur atom in the side chain as shown by deuterium-labeling experiments. Some Z isomers showed stronger protective effects in mice infected by Escherichia coli O-111 and more potent synergistic activities with cefotiam in mice infected by Proteus vulgaris GN4815 than did the naturally occurring E isomers. The decomposition rates of the Z isomers in mouse kidney homogenates were about 3-fold slower than those of the E isomers.
Asunto(s)
Tienamicinas/síntesis química , Animales , Bioensayo , Escherichia coli/efectos de los fármacos , Infecciones por Escherichia coli/tratamiento farmacológico , Indicadores y Reactivos , Isomerismo , Espectroscopía de Resonancia Magnética , Ratones , Infecciones por Proteus/tratamiento farmacológico , Proteus vulgaris/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Relación Estructura-Actividad , Tienamicinas/farmacología , Tienamicinas/uso terapéuticoRESUMEN
The stereochemical course of dehydrogenation catalyzed by acyl-CoA oxidase was investigated using the enzymes from rat liver peroxisomes and Candida lipolytica. Stearoyl-CoA and nonanoyl-CoA, stereospecifically labeled with deuterium at either C-2 or C-3, were incubated with the enzyme, the products were converted to methyl esters and their deuterium contents were measured by gas chromatography-mass spectrometry. The results suggested that acyl-CoA oxidase-catalyzed dehydrogenation occurred by anti-elimination of the pro 2R and pro-3R hydrogens of acyl-CoA.
Asunto(s)
Ácido Graso Desaturasas/metabolismo , Oxidorreductasas/metabolismo , Acilcoenzima A/metabolismo , Acil-CoA Oxidasa , Animales , Candida/enzimología , Fenómenos Químicos , Química , Cromatografía de Gases y Espectrometría de Masas , Hígado/enzimología , Conformación Molecular , RatasRESUMEN
Six components of new cephem antibiotics, cephabacin M1-6, were isolated from the culture filtrate of Xanthomonas lactamgena YK-431 by various types of column chromatographies and preparative reverse-phase HPLC. Their structures were determined by spectroscopic analyses and degradation studies. They consist of 7-methoxydeacetylcephalosporin C as a nucleus and a tri- to heptapeptide including a new amino acid, which is bound at the 3-position with an ester bond.
Asunto(s)
Antibacterianos/aislamiento & purificación , Cefalosporinas/aislamiento & purificación , Fenómenos Químicos , Química , Conformación Molecular , EspectrofotometríaRESUMEN
Fifteen components of new antibiotics, cephabacins, were isolated from the culture filtrates of Lysobacter lactamgenus YK-90, Xanthomonas lactamgena YK-280 and X. lactamgena YK-278. They were purified by column chromatography using cation-exchange resins, activated carbon, high porous resins and cation-exchange Sephadex and by preparative reverse-phase HPLC. The basic, water-soluble antibiotics were characterized as having a cephem skeleton and oligopeptide(s) as a side chain constituent from their spectroscopic analyses and amino acid analyses.
Asunto(s)
Cefalosporinas/aislamiento & purificación , Fenómenos Químicos , Química , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Xanthomonas/metabolismoRESUMEN
Two new nucleotide antibiotics, fosfadecin and fosfocytocin, have been isolated from the culture filtrates of Pseudomonas viridiflava PK-5 and Pseudomonas fluorescens PK-52, respectively. These antibiotics were purified by column chromatographies using adsorption, gel filtration and ion exchange resins. On the basis of the spectroscopic and degradation studies, the chemical structures of fosfadecin and fosfocytocin were determined. These antibiotics were either enzymatically or chemically hydrolyzed to generate fosfomycin and a new antibiotic, fosfoxacin, which are also produced in the culture filtrates. They showed antibacterial activity against Gram-positive and Gram-negative bacteria. The antibacterial activity of these nucleotide antibiotics was weaker than that of fosfomycin and fosfoxacin.
Asunto(s)
Antibacterianos/aislamiento & purificación , Bacterias/efectos de los fármacos , Pseudomonas/metabolismo , Adenosina Difosfato/análogos & derivados , Adenosina Difosfato/análisis , Adenosina Difosfato/aislamiento & purificación , Adenosina Difosfato/farmacología , Adenosina Difosfato/uso terapéutico , Animales , Antibacterianos/análisis , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Cromatografía , Citidina Difosfato/análogos & derivados , Citidina Difosfato/análisis , Citidina Difosfato/aislamiento & purificación , Citidina Difosfato/farmacología , Citidina Monofosfato/análogos & derivados , Citidina Monofosfato/análisis , Citidina Monofosfato/aislamiento & purificación , Citidina Monofosfato/farmacología , Infecciones por Escherichia coli/tratamiento farmacológico , Fermentación , Fosfomicina/análisis , Fosfomicina/aislamiento & purificación , Fosfomicina/farmacología , Hidrólisis , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Pseudomonas/clasificación , Infecciones Estafilocócicas/tratamiento farmacológicoRESUMEN
A new pyrrole-amidine antibiotic TAN-868 A was isolated from the culture broth of Streptomyces idiomorphus sp. nov. Its chemical structure was determined by spectroscopic analyses and degradation studies to be 4-[(2S,4R)-4-hydroxy-5-iminoprolyl]amino- N-(2-amidinoethenyl)-2-pyrrolecarboxamide. The antibiotic is active against bacteria, fungi and a protozoan, and has cytotoxic activity against murine tumor cells. DNA thermal denaturation studies suggest that TAN-868 A preferentially interacts with AT rich regions of double-stranded DNA.
Asunto(s)
Antibacterianos , Antibacterianos/aislamiento & purificación , Antibacterianos/metabolismo , ADN/metabolismo , Espectroscopía de Resonancia Magnética , Desnaturalización de Ácido Nucleico , Poli A/metabolismo , Poli T/metabolismo , Pirroles/aislamiento & purificación , Pirroles/metabolismo , Streptomyces/análisis , Relación Estructura-ActividadRESUMEN
New monocyclic beta-lactam antibiotics, formadicins A, B, C and D, were isolated from the culture filtrate of Flexibacter alginoliquefaciens sp. nov. YK-49 by various types of column chromatography and preparative reverse-phase HPLC. Their structures were determined by spectroscopic analyses and degradation studies. They have a nocardicin-type skeleton and a formylamino group at the 3- or 12-position. Formadicins A and B each have a D-glucuronide moiety and give formadicins C and D, respectively, upon hydrolysis using beta-D-glucuronidase.
Asunto(s)
Antibacterianos/aislamiento & purificación , Lactamas , beta-Lactamas , Antibacterianos/farmacología , Fenómenos Químicos , Química , beta-Lactamasas/farmacologíaRESUMEN
New 7-methoxycephem antibiotics were found in culture filtrates of a bacterium isolated from a plant and named cephabacin M1-6. They are the first members of 7-methoxycephem antibiotics of bacterial origin. The producing organism was taxonomically characterized and identified as Xanthomonas lactamgena YK-431; other strains of this species have recently been reported to produce cephabacin F and H group antibiotics. Cephabacin M1-6 exhibited moderate antibacterial activity against Gram-negative and Gram-positive bacteria. Cephabacin M1-6 were as stable as cephamycin C to cephalosporinases. They showed inhibitory activity against a cephalosporinase of Proteus vulgaris GN 4413. The mode of action of cephabacin M1 was examined using Escherichia coli and Bacillus subtilis as test organisms; primary lethal targets of cephabacin M1 are penicillin-binding protein (PBP) 1 in E. coli and PBP 4 in B. subtilis.
Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas , Cefalosporinas/farmacología , Hexosiltransferasas , Peptidil Transferasas , Xanthomonas/metabolismo , Antibacterianos/aislamiento & purificación , Proteínas Portadoras/metabolismo , Cefalosporinas/aislamiento & purificación , Escherichia coli/metabolismo , Fermentación , Muramoilpentapéptido Carboxipeptidasa/metabolismo , Proteínas de Unión a las Penicilinas , Peptidoglicano/biosíntesis , Relación Estructura-Actividad , Inhibidores de beta-Lactamasas , beta-Lactamasas/farmacologíaRESUMEN
Two new indolocarbazole alkaloids, TAN-999 and TAN-1030A, were isolated from culture broths of Nocardiopsis dassonvillei C-71425 and Streptomyces sp. C-71799, respectively. Their structures were elucidated on the basis of their reactions, spectroscopic analyses and in particular, comparison of spectral data with that of staurosporine. These metabolites induced spreading of a murine macrophage cell line, Mm 1. They also augmented the phagocytic activity, Fc gamma receptor expression and beta-glucuronidase activity of murine macrophage cell lines, Mm 1 and J774A.1. When proteose-peptone elicited peritoneal macrophages from mice were incubated with these metabolites for 2 days, the phagocytosis-dependent respiratory burst of these cells was enhanced. Similar enhancement was also observed when the peritoneal macrophages in mice were modulated by intraperitoneal administration of these metabolites. These results reveal that TAN-999 and TAN-1030A can activate macrophage functions in mice.
Asunto(s)
Alcaloides/farmacología , Carbazoles , Indoles , Activación de Macrófagos/efectos de los fármacos , Alcaloides/aislamiento & purificación , Animales , Antígenos de Diferenciación/metabolismo , Línea Celular , Femenino , Fermentación , Glucuronidasa/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Microscopía Electrónica de Rastreo , Estructura Molecular , Fagocitosis/efectos de los fármacos , Receptores Fc/metabolismo , Receptores de IgG , Análisis Espectral , Streptomyces/clasificación , Streptomyces/metabolismo , Streptomyces/ultraestructuraRESUMEN
Thiotropocin, a new sulfur-containing 7-membered-ring antibiotic, was isolated from a culture broth of Pseudomonas sp. CB-104. The antibiotic occurs as orange or yellowish orange needles and has the molecular formula C8H4O3S2. It is active against Gram-positive and Gram-negative bacteria, some phytopathogens and mycoplasma.
Asunto(s)
Antibacterianos/aislamiento & purificación , Pseudomonas/metabolismo , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Fenómenos Químicos , Química , Fermentación , Pseudomonas/clasificación , Tropolona/análogos & derivados , Tropolona/síntesis química , Tropolona/aislamiento & purificaciónRESUMEN
The structures of 15 new cephem antibiotics, cephabacin F1-9 and H1-6, were determined by their spectroscopic analyses and decomposition studies. They are consisted of a cephalosporin nucleus and a di, tri or tetrapeptide including a new amino acid which is bound at the position 3 with an ester bond. The components, F1-9, showed unique biological activities by the presence of a formylamino group at the position 7.
Asunto(s)
Cefalosporinas , Fenómenos Químicos , Química , Hidrólisis , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Conformación MolecularRESUMEN
Novel iron-containing peptide antibiotics, ferrocins A, B, C and D, have been isolated from the culture filtrate of Pseudomonas fluorescens YK-310. These antibiotics were purified by butanol extraction, followed by column chromatography using adsorption resin, silica gel and preparative reverse-phase HPLC. The structures of ferrocins were elucidated using spectroscopic and degradative methods. Ferrocins contain three hydroxamate moieties per ferric ion which forms an octahedral iron complex.
Asunto(s)
Antibacterianos , Antibacterianos/aislamiento & purificación , Péptidos , Pseudomonas/metabolismo , Secuencia de Aminoácidos , Animales , Antibacterianos/química , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos , Compuestos Férricos/química , Compuestos Férricos/aislamiento & purificación , Compuestos Férricos/farmacología , Hierro/análisis , Ratones , Datos de Secuencia Molecular , Péptidos Cíclicos/química , Péptidos Cíclicos/aislamiento & purificación , Péptidos Cíclicos/farmacologíaRESUMEN
New naphthacenecarboxamide antibiotics, TAN-1518 A and B, were isolated from a culture broth of Streptomyces sp. AL-16012. Their structures were elucidated from their reactions and from spectroscopic analyses. The relaxation of supercoiled pBR322 DNA by calf thymus DNA topoisomerase I was inhibited by these metabolites as potently as by camptothecin. However, the decatenation of kinetoplast DNA by calf thymus DNA topoisomerase II was little affected by these agents. The major metabolite, TAN-1518 A, strongly suppressed the growth of various murine and human tumor cells, inducing apoptosis. Unlike camptothecin, TAN-1518 A did not stimulate cleavable complex formation in the nuclei of CHO-K1 cells and had weak activity in intercalating into DNA strands. This metabolite arrested the growth of human tumor cell lines in G1 phase of the cell cycle. These results suggest that TAN-1518 A and B are novel antitumor agents targeting topoisomerase I.
Asunto(s)
Antibióticos Antineoplásicos/farmacología , Tetraciclinas/farmacología , Inhibidores de Topoisomerasa I , Animales , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/aislamiento & purificación , Apoptosis , Células CHO , División Celular/efectos de los fármacos , Cricetinae , Cricetulus , ADN de Neoplasias/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Fermentación , Células HeLa , Humanos , Ratones , Streptomyces/química , Streptomyces/clasificación , Tetraciclinas/química , Tetraciclinas/aislamiento & purificación , Células Tumorales CultivadasRESUMEN
A novel antifungal antibiotic, TAN-950 complex, was isolated from the culture filtrate of Streptomyces platensis A-136 (IFO 14603, FERM BP-1786). The water-soluble amphoteric substances in this complex were purified by chromatography using ion-exchange resins, QAE-Sephadex and adsorptive resins and were designated TAN-950 A and TAN-950 A-E mixture. The molecular formula of TAN-950 A was determined to be C6H7N2O4Na for the sodium salt. This new amino acid antibiotic showed antifungal activity against Candida albicans in vitro and in vivo, and had low toxicity in mice.
Asunto(s)
Antifúngicos/biosíntesis , Animales , Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Femenino , Fermentación , Isoxazoles/aislamiento & purificación , Isoxazoles/farmacología , Ratones , Streptomyces/clasificación , Streptomyces/metabolismoRESUMEN
Novel anti-Helicobacter pylori antibiotics, pyloricidins A, A1, A2, B, C and D were isolated from Bacillus sp. HC-70 and Bacillus sp. HC-72 by column chromatographies using adsorption and ion exchange resins. Their structures have been elucidated based on spectroscopic and degradation studies and shown to be peptide-like compounds. These compounds contained two unusual amino acids, viz., 5-amino-2,3,4,6-tetrahydroxyhexanoic acid and 3-amino-3-phenylpropionic acid (beta-phenylalanine). The structure-activity relationship studies suggested that 3-(5-amino-2,3,4,6-tetrahydroxyhexanoyl)amino-3-phenylpropionic acid moiety was essential for anti-H. pylori activity.
Asunto(s)
Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Bacillus/química , Péptidos , Aminoácidos/análisis , Antibacterianos/química , Cristalografía por Rayos X , Fermentación , Cromatografía de Gases y Espectrometría de Masas , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Rotación Óptica , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Relación Estructura-ActividadRESUMEN
A Gram-negative bacterium was found to produce new antibacterial antibiotics, sperabillins A, B, C and D, and the producing bacterium was characterized and identified as Pseudomonas fluorescens YK-437. Sperabillins were isolated by column chromatographies using cation-exchange resins, activated carbon and cation-exchange Sephadex, and preparative reverse-phase HPLC. Sperabillins showed antibacterial activity against Gram-negative and Gram-positive bacteria including antibiotic-resistant strains of Pseudomonas aeruginosa and Staphylococcus aureus. Sperabillin A inhibited DNA, RNA, protein, and cell wall biosynthesis in Escherichia coli. Sperabillins showed good protective effects in experimentally infected mice.
Asunto(s)
Antibacterianos/biosíntesis , Bacterias/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas fluorescens/metabolismo , Staphylococcus aureus/efectos de los fármacos , Amidinas/química , Amidinas/aislamiento & purificación , Amidinas/farmacología , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Proteínas Bacterianas/biosíntesis , Proteínas Bacterianas/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Medios de Cultivo , ADN Bacteriano/biosíntesis , ADN Bacteriano/efectos de los fármacos , Fermentación , Espectroscopía de Resonancia Magnética , Ratones , Peptidoglicano/biosíntesis , Peptidoglicano/efectos de los fármacos , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Pseudomonas fluorescens/clasificación , ARN Bacteriano/biosíntesis , ARN Bacteriano/efectos de los fármacos , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismoRESUMEN
Modification of sperabillins was carried out. The 2-amidinoethylamino moiety was removed by brief acidic hydrolysis. The 2,4-hexadienoyl moiety was hydrogenated to the hexanoyl moiety and this was cleaved by an enzymatic reaction using the cells of Pseudomonas acidovorans IFO 13582. The 2-amidinoethylamino and the 2,4-hexadienoyl moieties were replaced with other groups. The derivative which was prepared by condensation of two molar amounts of dehexadienoylsperabillin A with (E,E)-muconic acid showed better protective effects than sperabillin A against Gram-negative bacteria.
Asunto(s)
Antibacterianos/síntesis química , Amidinas/síntesis química , Amidinas/farmacología , Animales , Antibacterianos/farmacología , Dosificación Letal Mediana , Ratones , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadRESUMEN
Broadband dielectric measurements for blends of poly(vinyl pyrrolidone) (PVP) and ethylene glycol oligomer (EGO) from 0 to 40 wt % PVP were carried out at 25 degrees C in the frequency range from 20 Hz to 20 GHz. The EGOs used in this study were ethylene glycol (EG), diethylene glycol (2EG), and PEG400 (MW = 400). For the PVP-EG, -2EG, and -PEG400 blends, relaxation processes caused by the motion of EGO in the GHz range and the micro-Brownian motion of the PVP chain at 10 kHz-1 MHz were observed. Although the PVP-EGO blend is miscible, relaxation processes caused by the molecular motion of EGO and the local chain motion of PVP were observed individually. The relaxation time of the local chain motion of PVP showed a strong PVP concentration dependence and a solvent viscosity dependence, which are similar to those reported so far for the solutions in nonpolar solvents.
RESUMEN
Sperabillin A, 3-[[(3R,5R)-3-amino-6-[(2E,4Z)-2,4-hexadienoylamino]- 5-hydroxyhexanoyl]amino]propanamidine dihydrochloride, was polymerized on standing for several days under a highly humid atmosphere or in the presence of radical initiators. The average molecular weight of the polymers obtained could be regulated by changing the reaction conditions in the latter case. Spectral analyses of the polymers revealed that the 2,4-hexadienoyl moiety of sperabillins was polymerized in a free radical-initiated reaction. The polymers selectively inhibited the proliferation of human umbilical vein endothelial (HUVE) cells. Polymers having higher molecular weight showed stronger inhibition of HUVE cell proliferation. In addition, the polymers showed anti-tumor activity against B16 melanoma in vivo.