The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 46 , Issue 5
Showing 1-24 articles out of 24 articles from the selected issue
  • HIROAKI OHKUMA, KOJI TOMITA, YUTAKA HOSHINO, KIYOSHI SUZUKI, MASAMI HA ...
    1993 Volume 46 Issue 5 Pages 705-711
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Three new 5-lipoxygenase inhibitors, designated as BU-4601 A, B and C, were found in the fermentation broth of Streptomyces sp. strain No. AA2807. Their structures were identified as isodecyl, isoundecyl and isolauryl esters of 5-hydroxyanthranilic acid, respectively. Based on their structures, five related esters were synthesized and evaluated for biological activity as inhibitors of 5-lipoxygenase. Both naturally-occurring and chemically-synthesized compounds exhibited almost equal levels of 5-lipoxygenase inhibibory activities in vitro.
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  • TAKAYUKI AOYAMA, FUKIKO KOJIMA, TADAO YAMAZAK, TOCHIRO TATEE, FUMINORI ...
    1993 Volume 46 Issue 5 Pages 712-718
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Benastatin C, a new member of the benastatins, has been isolated from the culture broth of Streptomyces sp. MI384-DF12. The structure of benastatin C was elucidated as 2-decarboxybenastatin A by NMR studies. Benastatin D, 2-decarboxybenastatin B, was derived from benastatin B. Benastatins C and D showed inhibitory activities against human pi class glutathione S-transferase (GST π) and excellent stimulatory activities on the murine lymphocyte blastogenesis in vitro.
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  • MITSUHIRO UENO, MASAHIDE AMEMIYA, MASATOMI IIJIMA, MICHIYO OSONO, TORU ...
    1993 Volume 46 Issue 5 Pages 719-727
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    In order to develop a new class of immunomodulator we have searched for a low molecular weight inhibitors of cell adhesion to components of extracellular matrix (ECM), fibronectin (FN), laminin (LM) and collagen type IV (CL), and succeeded to find a group of novel antibiotics, named delaminomycins. Delaminomycins were isolated from the mycelium and cultured broth of Streptomyces albulus MJ202-72F3. It was purified by use of centrifugal partition chromatography (CPC), preparative reverse phase HPLC and Sephadex LH-20 and was obtained as a white powder. Delaminomycins with inhibitory activity for cell adhesion to ECM components suppressed immune responses in vitro and in vivo and exhibited antimicrobial activity on Gram-positive bacteria.
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  • KEIICHI ABE, MINORU YOSHIDA, SUEHARU HORINOUCHI, TERUHIKO BEPPU
    1993 Volume 46 Issue 5 Pages 728-734
    Published: May 25, 1993
    Released: April 19, 2006
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    Leptolstatin, a new inhibitor of the progression of Gl and G2 phases of the mammalian cell cycle, was discovered through a unique screening system, in which effects of microbial metabolites on the cell cycle progression of the cultured rat fibroblasts were monitored by flow cytometry. The new inhibitor was extracted from the fermentation broth of Streptomyces sp. SAM 1595 with ethyl acetate, and purified by silica gel column chromatography and HPLC. Leptolstatin showed a strong cytostatic effect on rat normal fibroblasts 3Y1 with an IC50 value of 0.4ng/ml, but its antimicrobial activity was very weak. A 24-hour treatment of the fibroblast cells with lOng/ml of leptolstatin caused an arrest at Gl or G2 phase, as determined by flow cytometry. When the G2-arrested cells were freed from leptolstatin, those containing 4C DNA entered a new S phase without intervening M phase, resulting in the formation of proliferative tetraploid cells.
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  • KEIICHI ABE, MINORU YOSHIDA, HIDEO NAOK, SUEHARU HORINOUCHI, TERUHIKO ...
    1993 Volume 46 Issue 5 Pages 735-740
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Leptolstatin, a product from Streptomyces sp. SAM 1595, is a gap phase-specific inhibitor of the mammalian cell cycle. Physico-chemical properties and spectrometric analyses showed that the structure of leptolstatin is (2Z, 6E, 8Z, 12E, 14E, 22E)-19, 24-dihydroxy-8, 10, 14, 16, 18, 20, 22-heptamethyl-17-oxo-2, 6, 8, 12, 14, 22-tetracosahexaen-5-olide.
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  • FLORENZ SASSE, HEINRICH STEINMETZ, GERHARD HÖFLE, HANS REICHENBAC ...
    1993 Volume 46 Issue 5 Pages 741-748
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A new cytostatic compound, rhizopodin, was isolated from the culture broth of the myxobacterium, Myxococcus stipitatus. The compound inhibited growth of various animal cell cultures without killing the cells. The ID50, measured by an MTT assay, was 12 - 30 ng/ml, depending on the cell line. Especially cells growing fibroblast-like showed typical morphological changes. They became larger and within hours formed long branching and reticular runners. These morphological changes were irreversible. Rhizopodin suppresses bleb formation in K-562 cells, and therefore could act by interacting with protein phosporylation.
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  • NORIKO TABATA, YASUKO SUZUMURA, HIROSHI TOMODA, ROKURO MASUMA, KATSUJI ...
    1993 Volume 46 Issue 5 Pages 749-755
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Humicola sp. FO-888, a soil isolate, was found to produce a series of new anticoccidial compounds. Five active compounds, designated xanthoquinodins Al, A2, A3, Bl and B2 were isolated from the fermentation broth of the producing strain by solvent extraction and HPLC. Xanthoquinodins inhibited the growth of Eimeria tenella in an in vitro assay system using BHK-21 cells as a host. No schizont in the cells was observed at concentrations of 0.02-0.2μg/ml for xanthoquinodins Al, A3, Bl and B2 and at 0.02μg/ml for xanthoquinodin A2.
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  • NORIKO TABATA, HIROSHI TOMODA, YOKO TAKAHASHI, KATSUJI HANEDA, YUZURU ...
    1993 Volume 46 Issue 5 Pages 756-761
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Streptomyces sp. WK-2955, a soil isolate, was found to produce a series of new anticoccidial compounds. Four active compounds, designated diolmycins A1, A2, B1 and B2, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography, gel filtration on Sephadex LH-20, and preparative HPLC. Diolmycins inhibited the growth of Eimeria tenella in an in vitro assay system using BHK-21 cells as a host. No schizont in the cells was observed at concentrations of 0.02-2.0μg/ml for diolmycin Al, at 0.2-2.0μg/ml for diolmycin A2, and at 20μg/ml for diolmycins Bl and B2.
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  • NORIKO TABATA, TOSHIAKI SUNAZUKA, HIROSHI TOMODA, TOHRU NAGAMITSU, YUZ ...
    1993 Volume 46 Issue 5 Pages 762-769
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structures of diolmycins Al, A2, Bl and B2, novel anticoccidial agents, were determined by spectroscopic analyses. Diolmycins Al and A2 are stereoisomers with the structure of 1 -(3-indolyl)-4-(p-hydroxyphenyl)-2, 3-butanediol. From the chemical synthesis of the erythro-isomer, the relative configurations of diolmycins A1 and A2 were determined to be the erythro- and threo-isomers, respectively. The stereoisomers, diolmycins B1 and B2, were also deduced to be erythro- and threo-1, 4-di-(p-hydroxyphenyl)-2, 3-butanediol, respectively.
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  • GILLES ETIENNE, BERNARD FABRE, ELISE ARMAU, FRÉDÉRIC LEG ...
    1993 Volume 46 Issue 5 Pages 770-776
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    CL307-24, a complex of new antibiotics has been isolated from the fermentation broth of Saccharopolyspora aurantiaca sp. nov. The complex was purified by cation-exchange and hydrophobic interaction chromatographies. It was then resolved as one major and three minor components by silica gel chromatography and HPLC.
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  • TETSUYA MATSUMOTO, MITSUO KAKU, NOBUHIKO FURUYA, TOSHIAKI USUI, SHIGER ...
    1993 Volume 46 Issue 5 Pages 777-784
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    We evaluated the effects of amphotericin B (AmB) against Pseudomonas aeruginosa (P. aeruginosa) infection in mice. Pretreatment with 2mg/kg of AmB 24 hours before infection significantly increased the survival rates of mice intraperitoneally infected with either P. aeruginosa or Escherichia coli. To evaluate the mechanism of this AmB-induced resistance to infection, we conducted a number of experiments. Peritoneal macrophages exposed in vitro to AmB showed superior bactericidal activity compared to that of control macrophages. Interleukin-1 production by peritoneal macrophages from mice pretreated with 2 mg/kg of AmB was significantly higher than that in control mice. Serum tumor necrosis factor level after intravenous injection of P. aeruginosa was also higher in mice pretreated with 2 mg/kg of AmB than in control mice. These data indicate that AmB induces resistance to P. aeruginosa in mice. Furthermore AmB-induced activation of peritoneal macrophages and their production of interleukin-1 and tumor necrosis factor appeared to play important roles in this phenomenon.
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  • TSUTOMU OIKAWA, HIROMI ASHING, MARIKO SHIMAMURA, MASAMI HASEGAWA, IKUO ...
    1993 Volume 46 Issue 5 Pages 785-790
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Here we describe the inhibitory effect of erbstatin, a specific tyrosine kinase inhibitor, on in vivo angiogenesis. Inhibition of angiogenesis was determined in a bioassay system involving chorioallantoic membranes of growing chick embryos. Erbstatin produced a dose-dependent inhibitory action on embryonic angiogenesis. This inhibition occurred at as small a dose as 10 ng/egg and the ID50 value was 80 ng/egg. To analyze this inhibition, in vitro experiments involving vascular endothelial cells were also performed. Erbstatin affected the proliferation of vascular endothelial cells, one of angiogenic components. This inhibition was dose-dependent, the IC50 value being 3.6 μM. These data indicate that erbstatin-sensitive tyrosine kinase(s) is involved in angiogenic endothelial cell proliferation, and that experiments involving erbstatin will provide an important clue to understand a mechanism of angiogenesis.
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  • TOSHIO OTANI
    1993 Volume 46 Issue 5 Pages 791-802
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Characterization of the secondary structure of the antitumor antibiotic C-1027 has been made from a comparison of C-1027 and its apoprotein by various analytical means. The results indicated the antibiotic to be abundant in β-structure by measurements of Fourier-transform infrared (FT-IR) spectroscopy and the circular dichroism (CD) spectrum, and by a prediction of the secondary structure based on the amino acid sequence of the peptide. In comparison of the IR spectra of their proteins in D2O, the apoprotein exhibited a faster H-D exchange than C-1027, indicating an increase in the "non-motile parts" of the β-sheets formed through the protein-chromophore interaction in holo-C-1027. The prediction of hydropathic index indicated the hydrophobic residues of the apoprotein to be predominantly located in the β-sheet structures, suggesting hydrophobic interaction in the binding between chromophore and apoprotein. Further, the interaction between chromophore and apoprotein was detected by a fluorescence method. The result showed the dissociation constant (Kd) to be 6.88 × 10-5 M, indicating that the chromophore is tightly bound to the protein moiety.
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  • TSUNEAKI HIDA, SHIGETOSHI TSUBOTANI, NOZOMI KATAYAMA, YASUNORI FUNABAS ...
    1993 Volume 46 Issue 5 Pages 803-812
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    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.
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  • MASAYA NAKATA, TETSURO TAMAI, YUKIKO MIURA, MITSUHIRO KINOSHITA, KUNIA ...
    1993 Volume 46 Issue 5 Pages 813-826
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Two new derivatives, 3''-epi-erythromycin A (2) and (9S)-11-dehydroxy-9-deoxo-9-hydroxy-11-oxoerythromycin A (3), have been synthesized by using glycosylation with glycal (Ferrier rearrangement), bromomethoxylation and bis(tributyltin) oxide-bromine oxidation as the key steps. Their antimicrobial activities were compared with those of erythromycin A (1).
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  • YUTAKA TAKEUCHI, TAKAAKI INOUE, MAKOTO SUNAGAWA
    1993 Volume 46 Issue 5 Pages 827-832
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structure and solution conformation of meropenem was examined by using 1H and 13C NMR spectroscopy and nuclear Overhauser enhancement experiments. Similar to the X-ray crystal structure, the close spacing of 1β-methyl substituent to the β-lactam ring and the accessible conformation of C-2 side chain in relation to the carbapenem skeleton was confirmed. The structure of the primary metabolite of meropenem by dehydropeptidase-I was shown to be the β-lactam ring-opened product by comparing the spectrpscopic data with those of meropenem, and confirmed by the preparation and structural analysis of its crystalline derivative. This metabolite existed as a mixture of 1-pyrroline and 2-pyrroline isomers, and the coexistence of two isomers at equilibrium in aqueous solution was observed by NMR.
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  • TAKAAKI OKITA, KIYOTO IMAE, TOSHIFUMI HASEGAWA, SEIJI IIMURA, SHINJI M ...
    1993 Volume 46 Issue 5 Pages 833-839
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Cephalosporins having a catechol through a variety of linkages to the C3 position and a different C7 side chain were prepared. Among them, 3-(catechol-4-ylcarbonyloxy)methylcephalosporin (14) and 3-[(E)-3-(catechol-4-ylcarbonyloxy)-l-propen-l-yl]cephalosporin (10) showed excellent activity against Gram-negative activity including ceftazidime-resistant Escherichia coli, Pseudomonas aeruginosa, Xanthomonas maltophilia and Pseudomonas cepacia.
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  • KIYOTO IMAE, SEIJI IIMURA, TOSHIFUMI HASEGAWA, TAKAAKI OKITA, MINORU H ...
    1993 Volume 46 Issue 5 Pages 840-849
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Two groups of cephalosporins substituted with a variety of heterocyclic catechols in the C3 side chain were synthesized. One is a group of 3-(heterocyclic catechol-substituted methyl)cephalosporins and another is 3-[(E)-3-heterocyclic catechol-substituted l-propen-l-yl]cephalosporins. Cephalosporins in the latter group showed higher in vivo efficacies than those in the former group having the same heterocyclic catechol, especially against Pseudomonas aeruginosa A9843A, although there was no significant difference between their in vitro activity. Among the latter group, the 5, 6-dihydroxybenzimidazole derivative (6e) and the 2, 6-dihydro-7-hydroxy-6-oxo-isoquinoline derivative (6b) showed much higher activity than ceftazidime (CAZ) and imipenem (IPM) against P. aeruginosa A9843A both in in vitro and in vivo studies.
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  • SEIJI IIMURA, KIYOTO IMAE, TOSHIFUMI HASEGAWA, TAKAAKI OKITA, MASAMI T ...
    1993 Volume 46 Issue 5 Pages 850-857
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    7-[(Z)-2-(2-Aminothiazol-4-yl)-2-methoxy-(or hydroxy)-iminoacetamido]-3-[propen-l-yl]-cephalosporins having a variety of heterocyclic catechol in 3-position of the propenyl group were synthesized. Among them, 6, 7-dihydroxyisoquinoline derivatives, 2a and 2b, showed very high and prolonged blood levels after intramuscular administration to mice and higher in vivo antibacterial activity than expected from their in vitro activity. The former cephalosporin (2a) gave wellbalanced in vitro and in vivo antibacterial spectra including anti-methicillin-resistant Staphylococcus aureus (MRSA) activity. The latter cephalosporin (2b) also showed good in vitro and in vivo activities against Gram-positive bacteria, especially against S. aureus A15036, a strain of MRSA, the in vivo activity being comparable to vancomycin but was lacking in anti-pseudomonal activity.
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  • MIHO TANAKA, YASUHIRO HORI, HIROTSUGU UEDA, MASAMI EZAKI, TOSHIO GOTO, ...
    1993 Volume 46 Issue 5 Pages 858-860
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • M. CHU, R. YARBOROUGH, J. SCHWARTZ, M. G. PATEL, A. C. HORAN, V. P. GU ...
    1993 Volume 46 Issue 5 Pages 861-865
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • MASAMI OGASAWARA, NOBUAKI NARUSE, ATSUKO YOSHIMURA, YASUTARO HAMAGISHI ...
    1993 Volume 46 Issue 5 Pages 866-868
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • JANICE L. DOULL, STEPHEN W. AYER, AMRIT K. SINGH, PIERRE THIBAULT
    1993 Volume 46 Issue 5 Pages 869-871
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • HIROSHI TOMODA, HIDETOSHI KUMAGAI, HARUO TANAKA, SATOSHI OMURA
    1993 Volume 46 Issue 5 Pages 872-874
    Published: May 25, 1993
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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