The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 36, Issue 8
Displaying 1-23 of 23 articles from this issue
  • MASAHITO NAKAYAMA, SHIGERU KIMURA, TOSHIMI MIZOGUCHI, SOHEI TANABE, AK ...
    1983 Volume 36 Issue 8 Pages 943-949
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    Two new carbapenem antibiotics, carpetimycins C and D have been isolated from the culture broth of Streptomyces sp. KC-6643, which produced carpetimycins A and B. The structures of carpetimycins C and D have been determined to be (5R, 6R)-3-[2-acetamidoethyl-(R)-sulfinyl]-6-(1-hydroxy-1-methylethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid and (5R, 6R)-3-[2-acetamidoethyl-(R)-sulfinyl]-6-(1-hydroxysulfonyloxy-1-methylethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, respectively. Studies on the fermentation, isolation and physico-chemical properties of these antibiotics are also described.
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  • T. F. BRODASKY, D. W. STROMAN, A. DIETZ, S. MIZSAK
    1983 Volume 36 Issue 8 Pages 950-956
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    U-56, 407, a bright yellow, crystalline antibiotic was isolated from fermentations of Streptomyces hagronensis (strain 360). This antibiotic was extracted from fermentation broths with halogenated hydrocarbons and purified by silica gel chromatography and crystallization. U-56, 407 is active in vitro against Gram-positive bacteria but not Gram-negative organisms. It failed to demonstrate in vivo activity in experimentally infected mice. Physical-chemical characterization of U-56, 407 supports a molecular formula of C29H32N2O7 and a structure related to the antibiotic asukamycin.
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  • I. TAXONOMY OF PRODUCING ORGANISM AND FERMENTATION
    AKIO TORIKATA, RYUZOU ENOKITA, TAKAO OKAZAKI, MUTSUO NAKAJIMA, SEIGO I ...
    1983 Volume 36 Issue 8 Pages 957-960
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    Strain No. 41042, an actinomycete isolated from a soil sample, was found to produce 5-azacytidine and new antibiotics, mycoplanecins. Yellowish brown to yellowish orange color of colonies on agar media, formation of globose to subglobose sporangia bearing motile spores and presence of meso- and hydroxy-diaminopimelic acid and glycine in the cell wall ascribed this strain to genus Actinoplanes. From its morphological, cultural and physiological characteristics, this strain was determined to be a new subspecies of Actinoplanes awajinensis and designated as A. awajinensis subsp. mycoplanecinus subsp. nov. Production of mycoplanecins was carried out by conventional submerged culture: the highest antibiotic titer obtained was 145 μg/ml.
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  • II. ISOLATION, PHYSICO-CHEMICAL CHARACTERIZATION AND BIOLOGICAL ACTIVITIES OF MYCOPLANECIN A
    MUTSUO NAKAJIMA, AKIO TORIKATA, YOSHIKAZU ICHIKAWA, TOSHIAKI KATAYAMA, ...
    1983 Volume 36 Issue 8 Pages 961-966
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    New antibiotics, mycoplanecins, were found in the culture broth of an actinomycete identified as Actinoplanes awajinensis subsp. mycoplanecinus subsp. nov. Mycoplanecin complex was extracted with organic solvents both from the culture filtrate and mycelium and purified by column chromatography on silica gel and Florisil. Mycoplanecin A, a major component, was separated by high performance liquid chromatography on Prep PAK-500/C18 column. The physico-chemical characterization revealed that mycoplanecin A was a new cyclic peptide antibiotic. Mycoplanecins exhibited strong activities primarily against mycobacteria and related microorganisms.
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  • III. STRUCTURAL DETERMINATION OF MYCOPLANECIN A
    MUTSUO NAKAJIMA, AKIO TORIKATA, HIDETSUNE TAMAOKI, TATSUO HANEISHI, MA ...
    1983 Volume 36 Issue 8 Pages 967-975
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    The structure of mycoplanecin A was determined by the analysis of chemical degradation products and by mass and 1H and 13C NMR spectrometries. Mycoplanecin A is a new cyclic peptide antibiotic composed of mol each of α-ketobutyric acid, glycine, L-leucine, L-proline, L-2-amino-5-methylhexanoic acid, N-methyl-D-leucine, N-methyl-L-threonine, methyl-L-proline and ethyl-L-proline and two mol of N-methyl-L-valine. Among these components, ethyl-L-proline is reported for the first time as a component of natural products. A newly developed mass analysis has been introduced for the differentiation of α-amino acid and its N-methyl derivative.
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  • K. ECKARDT, D. TRESSELT, W. IHN, M. KAJTÁR, J. ÁNGY&Aacu ...
    1983 Volume 36 Issue 8 Pages 976-979
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    By spectral (UV-VIS, IR, NMR, MS and CD) methods the quinone antibiotics sarubicin A and U-58, 431 were shown to have identical constitution and stereochemistry. Chiroptical data and their theoretical analysis have settled the common absolute configuration as 5S, 6R, 8R, 10R.
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  • STRUCTURE DETERMINATION OF MILBEMYCINS D, E, F, G, H, J AND K
    HIROSHI MISHIMA, JUNYA IDE, SHIGEKI MURAMATSU, MICHIHISA ONO
    1983 Volume 36 Issue 8 Pages 980-990
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    The milbemycins, a group of potent, broad-spectrum antiparasitic and pesticidal agents, are architecturally novel antibiotics of 16-membered macrocyclic lactone. Seven new milbemycin analogues designated as milbemycins D, E, F, G, H, J and K were isolated from the fermentation broth of the mutant strain of Streptomyces hygroscopicus subsp. aureolacrimosus. The structural determination of these new components was made mainly by comparing with mass spectra, and 1H and 13C NMR spectra of milbemycin α- and β-series previously published from our laboratory. Milbemycins D, E, F, G and H have characteristically an isopropyl side chain at C-25 which differs from the known milbemycin family bearing methyl or ethyl group at C-25. Milbemycins J and K possess a ketone group at C-5 instead of a hydroxyl or methoxy group. A part from X-ray crystallography, the R-configuration of the hydroxyl group at C-5 could be best explained both by application of CD allylic benzoate method to the p-N, N-dimethylaminobenzoate of milbemycin D and by comparison of the specific rotation of milbemycin D itself and its acetate with the epimeric isomers at C-5.
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  • STUDIES ON THE BIOSYNTHESIS OF MILBEMYCINS α2, α4 AND D USING 13C LABELED PRECURSORS
    MICHIHISA ONO, HIROSHI MISHIMA, YO TAKIGUCHI, MICHIYA TERAO, HISAYOSHI ...
    1983 Volume 36 Issue 8 Pages 991-1000
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    The biosynthetic origins of the carbon skeleton of milbemycins α2, α4 and D were studied. 13C Labeled antibiotics, milbemycins α2, α4 and D, were isolated from the culture broth of Streptomyces hygroscopicus subsp. aureolacrimosus strain Au-3 after feeding [1-13C]acetate, [1-13C]-propionate, [3-13C]propionate, [1-13C]isobutyrate, DL-[2-13C]valine and L-[methyl13C]methionine, and 13C NMR spectra of the antibiotics thus obtained were measured. It was revealed that the carbon skeleton, except for carbon 25, of milbemycins α2, α4 and D are derived from seven acetate units and five propionate units. It was also shown that the methyl, ethyl and isopropyl groups at carbon 25 in milbemycins αa, a, and D are derived from acetate, propionate and isobutyrate or DL-valine, respectively, and the methyl carbon of the methoxy group at carbon 5 in milbemycins α2 and α4 was enriched by L-[methyl13C]methionine.
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  • ANDRZEJ CZERWINSKI, HANNA WOJCIECHOWSKRA, RYSZARD ANDRUSZKIEWICZ, JOLA ...
    1983 Volume 36 Issue 8 Pages 1001-1006
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    Syntheses of the peptides with sequences postulated for active and inactive isomer of edeine D were carried out. The peptides obtained were identical with natural product in regard to chromatographic and electrophoretic properties. Biological data for synthesized compounds confirmed that in active and inactive isomer isoserine is linked with the α- or β-amino group of α, β-diaminopropionic acid, respectively.
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  • ALESSANDRO COSTA, GIUSEPPE A. BOTTA
    1983 Volume 36 Issue 8 Pages 1007-1012
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    Among the different mechanisms by which bacteria are resistant to β-lactam antibiotics, three are of major interest: production of β-lactamase, modifications of the target penicillin-binding proteins (PBPs) and decreased permeability. Cefotaxime (CTX) is a recently synthesized cephalosporin derivative, active against β-lactamase producing Gram-negative bacteria and possessing in the acylamino side chain a methoxyimino group in the syn-configuration. It has been compared for affinity to PBPs and penetration ability with its isomer possessing the same group in the anti-configuration and the corresponding demethoxyimino derivative. The anti-isomer, although resistant to β-lactamase, is devoid of antibacterial activity (MIC forEscherichia coli higher than 500μg/ml). The affinities of CTX and its analogues for the PBPs of several strains of E. coli have been determined in vivo and in vitro by competition experiments using intact cells and bacterial envelopes, respectively. Only minor differences in the affinity for the target PBPs were detected in vitro. However, in vivo studies proved that the 50% saturating concentrations for the PBPs were more than 100-fold higher for the anti-isomer than for CTX. The reported results suggest that a very simple structural modification of the CTX molecule greatly decreases the penetration ability of the antibiotic through the outer cell layers, thus dramatically affecting its antibacterial properties.
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  • SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF NEW 7β-[(Z)-2-ALKOXYIMINO-2-(2-AMINOTHIAZOL-4-YL)ACETAMIDO]-CEPHALOSPORINS WITH A TETRAZOLOPYRIDAZINE AT THE 3-POSITION
    MARCO ALPEGIANI, FERRUCCIO CASABUONA, RAFFAELLO GIORGI, GIULIANO NANNI ...
    1983 Volume 36 Issue 8 Pages 1013-1019
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    The synthesis and in vitro activity of 7β-[(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl) acetamido]cephalosporins with a tetrazole[1, 5-b]pyridazine at the 3-position are described. These cephalosporins showed excellent activity against Gram-negative bacteria, including β-lactamas producing strains. The most interesting compound of the series was 7β-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetamido]-3-(8-carboxytetrazolo[1, 5-b]pyridazin-6-yl)-thiomethyl-3-cephem-4-carboxylic acid (9, FCE20485) because of its extraordinarily long half-life and marked in vivoactivity.
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  • I. CSENDES, B. W. MÜLLER, W. TOSCH
    1983 Volume 36 Issue 8 Pages 1020-1033
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    Cephalosporins with a 7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2-oxyiminoacetamidol side chain were synthesized and their in vitro inhibitory potency was established. The compounds exhibit a strong antibacterial activity against various Gram-positive and Gram-negative bacteria. The antimicrobial activity is related to the oxime-substituent R1 and the C-3 substituent R2. Selected amino- 1, 2, 4-thiadiazolyl-cephems 1 show a prolonged half-Life in mice.
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  • TETSUO MIYADERA, YUKIO SUGIMURA, TOSHIHIKO HASHIMOTO, TERUO TANAKA, KI ...
    1983 Volume 36 Issue 8 Pages 1034-1039
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    The synthesis and in vitro antimicrobial activity of a new synthetic carbapenem, (5R, 6S)-6-[(R)-1-hydroxyethyl]-2-[(S)-l-acetimidoylpyrrolidin-3-ylthio]-l-carbapen-2-em-3-carboxylic acid (RS-533), are described. The MIC values of related penems and carbapenems are also given for comparison with those of the new carbapenem.
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  • HIROSHOI OGAWA, SATOSH IMAI, TOSHIKATSU SHIMIZU, ATSUYUKSAI SOTOH, MIC ...
    1983 Volume 36 Issue 8 Pages 1040-1044
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    Cosynthesis in mixed culture and protoplas fusion of non-producing mutants of Streptomyces hygroscopicuws which may produce biosynthetic intermediates of bialaphos(AMPBA) weres tudied. Non-producing mutants were obtained by mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine(NTG) treatment, and six stable non-producing mutants were used for cosynthesis and protoplast fusion studies. The biosynthetic block sites of the non-producers were consistent with studies of the biosynthetic pathway of AMPBA.
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  • ENHANCEMENT OF HOST RESISTANCE TO MICROBIAL INFECTION IN MICE
    YASUHIRO MINE, YOSHIKO YOKOTA, YOSHIMI WAKAI, SHIGEMI FUKADA, MINORU N ...
    1983 Volume 36 Issue 8 Pages 1045-1050
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    The protective effect of an immunoactive peptide, D-lactoyl-L-alanyl-γ-D-glutamyl-(L)-meso-diaminopimelyl-(L)-glycine (FK-156) and a related compound, heptanoyl-γ-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alanine (FK-565) was determined in mice with various kinds of microbial infections. FK-156 and FK-565 were given to mice either subcutaneously or orally before challenge. The drugs enhanced significantly the defense of mice against acute systemic infections induced by various extracellular and facultative intracellular organisms, and subcutaneous abscess by Staphylococcus aureus. The protective effect of these drugs against Escherichia coli infection differed considerably depending on the route of administration; FK-156 was only effective by the parenteral route; however, FK-565 was effective by both parenteral and oral routes. After subcutaneous dosing with FK-156, the enhancement of host defense of mice against E. coli infection was more rapid than against Listeria infection. The enhancing effects of FK-156 and FK-565 on host defense of mice against pseudomonal infection was more potent than other immunoactive drugs.
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  • RESTORATION OF HOST RESISTANCE TO MICROBIAL INFECTION IN IMMUNOSUPPRESSED MICE
    YOSHIKO YOKOTA, YASUHIRO MINE, YOSHIMI WAKAI, YUJI WATANABE, MINORU NI ...
    1983 Volume 36 Issue 8 Pages 1051-1058
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    The immunoactive peptides, FK-156 and its analogue, FK-565 were evaluated in various models of mice immunosuppressed with cyclophosphamide, hydrocortisone, mitomycin C, carrageenan and tumor cells. Treatment with FK-156 (subcutaneous) and FK-565 (oral) markedly restored host defense ability against microbial infection. The therapeutic effect of ticarcillin or gentamicin alone against pseudomonal infection in cyclophosphamide- and hydrocortisone-treated mice and tumor-bearing mice was much lower than in normal mice. The therapeutic effect of these antibiotics against pseudomonal infection in immunosuppressed mice was enhanced markedly by combined use with FK-156. The killing ability of macrophages and polymorphonuclear leukocytes of the immunosuppressed mice was also markedly enhanced by dosing with FK-156.
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  • ENHANCEMENT OF HOST DEFENSE MECHANISMS AGAINST INFECTION
    YASUHIRO MINE, YUJI WATANABE, SHUICHI TAWARA, YOSHIKO YOKOTA, MINORU N ...
    1983 Volume 36 Issue 8 Pages 1059-1066
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    We investigated the effect of immunoactive peptides. FK-156 and FK-565 on host defense mechanisms against microbial invasion. It was shown that these drugs given to normal mice increased the counts of phagocytes in both peripheral blood and peritoneal cavity, and enhanced the chemotactic, phagocytic and killing activities of peritoneal macrophages and polymorphonuclear leukocytes, and stimulated the phagocytic function of the reticuloendothelial system. Enhanced host resistance to microbial infection by these immunoactive peptides might be induced by both increase in counts and enhancement of functions of phagocytes. FK-156 restored decreased counts and functions of phagocytes in mice immunosuppressed by cyclophosphamide, hydrocortisone or tumor. These findings suggest that these immunoactive peptides could be applied to prevent intractable infection in immunocompromised hosts.
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  • AKIRA YOSHIDA, TAKEO YAMADA, MASAHIKO HIRAMATSU, HIDENORI KIUCHI, SHIN ...
    1983 Volume 36 Issue 8 Pages 1067-1075
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
    Effect of peplomycin sulfate (PLM) on pulmonary fibrosis was examined. Hydroxyproline, uronic acid, proline hydroxylase (EC 1.14.11.2) and glucosamine 6-phosphate synthetase (EC 2.6.1.16) in lungs of hamsters treated with PLM were studied and compared with those of hamsters treated with bleomycin (BLM). PLM, when administered intraperitoneally, one injection daily for 10 consecutive days, at either a high-(5 mg/kg) or low-(2.8 mg/kg) dosage-level, caused no significant increase of lung hydroxyproline and uronic acid as compared with controls. BLM on the other hand effected a significant increase in lung hydroxyproline on the high-dosage level (5 mg/kg) but not on the low-dosage level (2.8 mg/kg). In contrast, when administering PLM intratracheally, the concentrations of hydroxyproline in lungs increased 20% over the control levels. A transient increase of proline hydroxylase and glucosamine 6-phosphate synthetase also occurred shortly after the instillation. These increases were also observed in the corresponding groups treated with BLM, which confirmed the previous observations by other investigators. However, the magnitude of the increase was relatively lower in those values of PLM as compared with those of BLM. These data suggested that (1) PLM, when administered with multiple dosages intraperitoneatly, showed no signiticant effect on the elevation of lung hydroxyproline; (2) PLM, when administered with a dose intratracheally, induced pulmonary fibrosis similar to that caused by BLM. However, the hydroxyproline accumulation in lungs of PLM-treated hamsters was less than in those of the BLM-treated; (3) The fibrotic effect on the lungs caused by either PLM or BLM was probably attributed to acceleration of the syntheses of collagen and acidic glycos-aminoglycans.
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  • DICK SCHIPPER
    1983 Volume 36 Issue 8 Pages 1076-1077
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
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  • W. T. BRADNER, C. A. CLARIDGE, J. B. HUFTALEN
    1983 Volume 36 Issue 8 Pages 1078-1079
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
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  • TAKESHI UCHIDA, MASAYA IMOTO, TORU MASUDA, KANJI IMAMURA, YOICHI HATOR ...
    1983 Volume 36 Issue 8 Pages 1080-1083
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
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  • YUJI MORI, MAKOTO SUZUKI, KAZUTAKA FUKUSHIMA, TADASHI ARAI
    1983 Volume 36 Issue 8 Pages 1084-1086
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
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  • HAMAO UMEZAWA, HIROYUKI IWASAWA, DAISHIRO IKEDA, SHINICHI KONDO
    1983 Volume 36 Issue 8 Pages 1087-1091
    Published: 1983
    Released on J-STAGE: April 12, 2006
    JOURNAL FREE ACCESS
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