The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 39 , Issue 9
Showing 1-23 articles out of 23 articles from the selected issue
  • I.ISOLATION, CHARACTERIZATION, DEGRADATION REACTIONS AND BIOLOGICAL PROPERTIES
    KLAUS HÜTTER, EKKEHARD BAADER, KLAUS FROBEL, AXEL ZEECK, KLAUS BA ...
    1986 Volume 39 Issue 9 Pages 1193-1204
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Viriplanin A, a new anthracycline antibiotic produced by Ampullariella regularis strain SE 47, was isolated ffom a raw product that demonstrated activity&gainst Herpes simplex viruses. Based on spectroscopic data, the structure of the aglycone, viriplanol, was deter-mined, and the antibiotic was fbund to contain the sugar moieties 2-deoxy-L-fucose, 4-O-mesaconoyl-L-diginose and decilonitrose. In solution viriplanin A is very unstable to light.
    The antibiotic belongs to the nogalamycin group and is related to arugomycin and decilorubicin.
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  • HIROSHI TOMODA, RIMIKO IWATA, YOKO TAKAHASHI, YUZURU IWAI, RUIKO OIWA, ...
    1986 Volume 39 Issue 9 Pages 1205-1210
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A new antibiotic, lustromycin, was isolated from the cultured broth of Streptomyces sp. SK-1071. It exhibits selective antibacterial activity against anaerobic bacteria including Clostridium sp. The molecular formula C32H38O13 as determined by high resolution mass spectrometry, and elemental analysis and the NMR spectrum suggest structural resemblance of this antibiotic to luminamicin, an anti-anaerobic antibiotic reported previously.
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  • SATOSHI OMURA, HIROSHI TOMODA, QIN MIN XU, YOKO TAKAHASHI, YUZURU IWAI
    1986 Volume 39 Issue 9 Pages 1211-1218
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Triacsins A and B, new inhibitors of acyl-CoA synthetase, were isolated from the cultured broth of Streptomyces sp, strain SK-1894. The structurally related compounds WS-1228 A and B, known as hypotensive vasodilators, were also found to inhibit acyl-CoA synthetase. The four compounds have in common a N-hydroxytriazene moiety in their structures. The IC50 values for triacsin A and WS-1228 A were 5.5 and 3.6μg/ml, respectively.
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  • TAXONOMY, PRODUCTION AND ENZYME INHIBITION
    SATOSHI OMURA, HIDEYO ISHIKAWA, HIROSHI KUGA, NOBUTAKA IMAMURA, SEIKO ...
    1986 Volume 39 Issue 9 Pages 1219-1224
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Adecypenol, which exhlbits potent inhibitory activity against calf intestinal adenosine Deaminase (EC 3.5.4.4), was isolated from the cultured broth ofStreptomyces sp. OM-3223. Adecypenol was classified as a semi-tight binding inhibitor. TheKi value against calf intestinal adenosine deaminase was 4.7×10-9 M. No acute toxicity of adecypenol was observed at 100 mg/kg in mice. Adecypenol exhibited no antimicrobial activity against various bacteria and fungi at the concentration of 1.0 mg/ml.
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  • I. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7β-[2-ARYL-2-(AMINOACETAMIDO)ACETAMIDO]-CEPHALOSPORINS
    MINORU FURUKAWA, MASAHIRO ARIMOTO, SHIGETAKE NAKAMURA, AKIO EJIMA, YOH ...
    1986 Volume 39 Issue 9 Pages 1225-1235
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis andin vitro structure-activity relationships of cephalosporins having dipeptides substituted with various aryl groups as the side chain at the C-7 position have been outlined. Of these compounds, 2-aminothiazol derivatives showed a broad spectrum of enhanced antibacterial activity, and 7β-[DL-2-(D-aminopropionamido)-2-(2-aminothiazol-4-yl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acid (9) was the most balanced of these active derivatives with respect to both Gram-positive and Gram-negative strains.
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  • II. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7β-[2-(ACYLAMINO)-2-(2-AMINOTHIAZOL-4-YL)ACETAMIDO]CEPHALOSPORINS
    MASAHIRO ARIMOTO, AKIO EJIMA, TOSHIFUMI WATANABE, HIROAKI TAGAWA, MINO ...
    1986 Volume 39 Issue 9 Pages 1236-1242
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Cephalosporin derivatives(I)substituted with a neutral, acidic or basic amino acid group as the terminal group attached to the 2-amino-2-(2-aminothiazol-4-yl)acetamido side chain at the C-7 position were synthesized, and the effect of each group on antibacterial activity was examined. The derivatives bearing an amidino or guanidino group showed broad spectra of antibacterial activity similar to those of cefotaxime, but they were relatively sensitive to β-lactamases.
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  • III. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7β-[2-(2-AMINOTHIAZOL-4-YL)-2-(SUBSTITUTED CARBAMOYLMETHOXYIMINO)ACETAMIDO]CEPHALOSPORINS
    MASAHIRO ARIMOTO, TAKESHI HAYANO, TSUNEHIKO SOGA, TOSHIYUKI YOSHIOKA, ...
    1986 Volume 39 Issue 9 Pages 1243-1256
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Syntheses or cephalosporins modified with a 7β-[2-(2-aminothiazo14-yl)-2-(substituted carbamoylmethoxyimino)acetamidol group at the C-7 position and with various hetero aromatics at the C-3 position are described. The effects of substituents on the carbamoyl group in the 7-side chain were investigated in order to improve antibacterial activity. Some of these compounds exhibited high antibacterial activity against Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa, as well as good resistance to β-lactamase,
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  • ATSUSHI MAKITA, YASUHIRO YAMADA, HIROSUKE OKADA
    1986 Volume 39 Issue 9 Pages 1257-1262
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    (+)-Patulolide A, a new macrolide isolated from a Penicillium urticae mutant, was syn-thesized from 12-hydroxydodecanoic acid.
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  • MASAYUKI YAMATO, TOMIO TAKEUCHI, HAMAO UMEZAWA, NOBUO SAKATA, HIDEMI H ...
    1986 Volume 39 Issue 9 Pages 1263-1269
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    In the biosynthesis of valanimycin, valine is mostly incorporated into the isobutyl moiety of the antibiotic. The α-substituted acrylic moiety of valanimycin is derived from alanine. However, a part of alanine is metabolized into valine, thus incorporated also into the isobutyl moiety. Anaerobic conditions and some reducing agents strongly inhibit the biosynthesis.
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  • MARY M. SHERMAN, C. RICHARD HUTCHINSON
    1986 Volume 39 Issue 9 Pages 1270-1280
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The effect of known precursors, their fluorinated analogs, and biochemical inhibitors on the production of the polyether antibiotic, lasalocid A (1), by resting cells of Streptomyces lasaliensis was determined to study the biochemistry and regulation of antibiotic biosynthesis in vivo.
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  • ING-KAE WANG, LEO C. VINING, JOHN A. WALTER, A. GAVIN MCINNES
    1986 Volume 39 Issue 9 Pages 1281-1287
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The proton noise decoupled 13C nuclear magnetic resonance spectrum of tetracycline hydrochloride prepared from Streptomyces aureofaciens cultures supplemented with [1-13C]-acetate and [2-13C]acetate showed enrichment of nine alternating ring carbons. In addition, a small enrichment of the carboxamide carbon by [1-13C]acetate was observed. The labelling patterns clearly demonstrated the polyketide origin of the tetracyclic nucleus. The 13C nuclear magnetic resonance spectrum of tetracycline hydrochloride derived from [1, 2-13C]acetate showed all 18 ring carbons as doublets with coupling constants appropriate for the incorporation of nine intact two-carbon precursors, confirming that head-to-tail condensation of C2 units had occurred. Absence of bond scission within the C2 units and a low level of uncoupled 13C in the carboxamide substituent indicated that when the organism is supplemented with acetate, malonyl coenzyme A used for tetracycline biosynthesis is formed by direct carboxylation of acetyl coenzyme A.
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  • MIKIO KITAHARA, KIYOTO ISHII, TAKESHI OKAZAKI, TAKAYOSHI HIDAKA, KIYOS ...
    1986 Volume 39 Issue 9 Pages 1288-1290
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    7-Hydroxyguanine, an antitumor purine-analog, reacted with ribose (or deoxyribose)-1-phosphate in the presence of purine nucleoside phosphorylase. We prepared 7-hydroxyguanine riboside and deoxyriboside using purine nucleoside phosphorylase from bovine spleen. Each nucleoside exhibits antitumor activity against mouse leukemia L1210 cells. The therapeutic effect of 7-hydroxyguanine deoxyriboside is superior to those of 7-hydroxyguanine and 7-hydroxyguanine riboside.
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  • MASAHIDE HASOBE, MINEO SANEYOSHI, KIYOSHI ISONO
    1986 Volume 39 Issue 9 Pages 1291-1297
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Guanine 7-N-oxide was shown to have synergistic activity in combination with neplanocin A against a rhabdovirus, infectious hematopoietic necrosis virus (IHNV), as reported previously. We examined further the antiviral activity of guanine 7-N-oxide in combination with other nucleoside antibiotics against IHNV. Synergism was seen between guanine 7-N-oxide and D-eritadenine or cordycepin. It is considered that compounds inhibiting RNA methylation show synergism with guanine 7-N-oxide.
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  • WILLIAM C. KRUEGER, LORAINE M. PSCHIGODA, ALBERT MOSCOWITZ
    1986 Volume 39 Issue 9 Pages 1298-1303
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Chartreusin binds cooperatively to poly(dA-dT)•poly(dA-dT)and poly(Dg-dC)•poly(dG-dC). Both the site-exclusion model and the specific site model yield cooperative binding constants of about 5×105M-1 and 3×105 M-1 for the AT and GC polymers, respectively, and the same stoichiometry and intrinsic binding constant for both polymers of 5 nucleotides per binding site and 3.1×104M-1, The Scatchard plot for calf thymus DNA is curved in the opposite sense from that of cooperative binding. These binding data did not fit the site-exclusion model with the cooperative binding parameter as a variable nor the specific site, negative-cooperative binding model The site-exclusion model with a cooperative binding parameter of unity yielded a binding constant of about 4×104M-1 and a stoichiometry of about 5 nucleotides per binding site. The same model for transfer and ribosomal RNA yielded binding constants of 5×103 M-1 and 7×103 M-1 and stoichiometries of about 13 and 6 nucleotides per binding site, respectively.
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  • HIROKAZU YAMAMOTO, KARL H. MAURER, C. RICHARD HUTCHINSON
    1986 Volume 39 Issue 9 Pages 1304-1313
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Streptomyces erythraeus strains were transformed efficiently with six different plasmid DNA vectors by a protocol that uses 0.2 mM Ca2+, 5 mM Mg2+ and 10% DMSO to enhance the stability of protoplasts to storage at -80°C and their transformability at 30°C. The primary thiostrepton-resistant (Thior) transformants for most vectors were unstable even when grown selectively. This instability did not appear to be due to incompatibility with indigenousS. erythraeus plasmids. Conversely, stable transformation was not the result of plasmid or host mutations. Transformation instability or plasmid copy number thus prevented successful shotgun-cloning of DNA that complemented theeryD mutation, which blocks the biosynthesis of erythromycin A, because only plasmid DNA without an insert could be isolated from a Thior Ery+ clone.
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  • PATRICIA LACROLX, MARC AUMERCIER, MARIE-LOUISE CAPMAU, FRANCOIS LE GOF ...
    1986 Volume 39 Issue 9 Pages 1314-1321
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Binding experiments were performed with both components of the pristinamycin complex (pristinamycin IA (PIA) and pristinamycin IIA (PIIA)) using ribosomes from sensitive and resistant Staphylococcus aureus. Fluorescence polarization was used to measure PIA binding. The results obtained show a direct correlation between inhibition, synergy and the enhancement of the affinity of PIA for its receptor in the presence of PIIA. The uptake of PIA by intact cells seems to be directly correlated with affinity between PIA and ribosomes, a phenomenon which is probably shared with the macrolide antibiotics.
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  • M. AUMERCIER, S. BOUHALLAB, M.-L. CAPMAU, F. LE GOFFIC
    1986 Volume 39 Issue 9 Pages 1322-1328
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    In vitro and in vivo studies are presented to test the hypothesis that the synergistic action of the pristinamycins is not due to a catalytic effect of pristinamycin IIA (PIIA) on the bacterial ribosome. We demonstrate that there is a proportionality between the quantity of PIIA bound on the ribosome and pristinamycin IA (PIA) retained by it. Moreover in vivo and
    in vivo experiments correlated to biological effects (growth and protein synthesis) demonstrate that pristinamycin IIA is tightly bound on 70S ribosome, which satisfactory explains the so called "lasting damage effect".
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  • YOSHINOBU YOSHIMURA, NAORU HAMAGUCHI, TAKATSUKA YASHIKI
    1986 Volume 39 Issue 9 Pages 1329-1342
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    In a separate study on the orally active acyloxymethyl esters (1) of 7[2-(2-aminothiazol-4-yl)acetamido]3-[[[1-(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thio]methyl]ceph-3-em-4-carboxylic acid (cefotiam, CTM), we have shown, by quantitative structure-oral bioavailability (BA) relation analysis, that the R2 group in the acyl group R2CO must have both an adequate lipophilicity (HANSCH's lipophilic parameter, π) and steric hindrance (TAFT's Es value). However, to satisfy these requirements, a complex alkyl group R2 must be employed, the ester of which is difficult to synthesize and has unique metabolic fate. In this study, we selected and prepared the 1-acyloxyethyl esters (2) of CTM instead of 1 to avoid R2 groups that are too complicated. We found that the esters (2) gave improved oral BAs over 1: the 1-(3-methylvaleryloxy) ethyl ester (2h) showed the highest peak plasma CTM level(Cmax) comparable to that obtained after subcutaneous injection of CTM. The 1-(cyclohexylacetoxy)ethyl ester (2t), the 1-(2-ethylbutyryloxy)ethyl ester(2j), and 2h showed BAs near 100%. For these esters (2), good correlations were also observed among the π, the Es values of R2, and the
    log Cmax and log BA in the analysis of the quantitative structure-oral bioavailability relation: an ester having an alkyl group as R2 with a π value of 3.07 or 3.08 and a Es value of-1.04 or -1.29 gave the highest Cmax or BA, respectively. As expected, the optimalπvalues are almost the same as those obtained with 1 but the optimal Es values are larger (Es=-2.07). Thus, it has been confirmed by preparing 1-acyloxyethyl esters (2) of CTM that the oral bioavailability of CTM can further be improved without preparing acyloxymethyl esters (1) with a complicated acyl group.
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  • KAZUO TSUZUKI, YUZURU IWAI, SATOSHI OMURA, HIDEKI SHIMIZU, NAKAO KITAJ ...
    1986 Volume 39 Issue 9 Pages 1343-1345
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • KEI-ICHI NUMATA, FUMI SATOH, MASAMI HATORI, TAKEO MIYAKI, HIROSHI KAWA ...
    1986 Volume 39 Issue 9 Pages 1346-1348
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • J. H. WILTON, C. D. RITHNER, G. C. HOKANSON, J. C. FRENCH
    1986 Volume 39 Issue 9 Pages 1349-1350
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • ETTORE PERRONE, MARCO ALPEGIANI, ANGELO BEDESCHI, FRANCO GIUDICI, FRAN ...
    1986 Volume 39 Issue 9 Pages 1351-1355
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • 7. THE ABSOLUTE CONFIGURATION OF 2-PHOSPHINOMETHYLMALIC ACID, A BIOSYNTHETIC INTERMEDIATE OF BIALAPHOS
    KUMIKO SHIMOTOHNO, HARUO SETO, NOBORU OTAKE, SATOSHI IMAI, ATSUYUKI SA ...
    1986 Volume 39 Issue 9 Pages 1356-1359
    Published: 1986
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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