The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 41 , Issue 10
Showing 1-28 articles out of 28 articles from the selected issue
  • I. DISCOVERY, TAXONOMY AND FERMENTATION
    MARIANNA JACKSON, JAMES P. KARWOWSKI, ROBERT J. THERIAULT, MARY L. MAU ...
    1988 Volume 41 Issue 10 Pages 1293-1299
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Phenelfamycins A, B, C, E, F and unphenelfamycin have been discovered in the fermentation broth of two soil isolates, designated AB 999F-80 and AB 1047T-33. These isolates were identified as strains of Streptomyces violaceoniger. The antibiotics were selected for their activity against anaerobic bacteria.
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  • II. ISOLATION AND STRUCTURE DETERMINATION
    J. E. HOCHLOWSKI, M. H. BUYTENDORP, D. N. WHITTERN, A. M. BUKO, R. H. ...
    1988 Volume 41 Issue 10 Pages 1300-1315
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A novel complex of elfamycin-type antibiotics has been isolated from submerged fermentation of either Streptomyces violaceoniger AB 999F-80 or Streptomyces violaceoniger AB 1047T-33. Antibiotics were extracted from the fermentation broth with ethyl acetate and from the mycelia with acetone. Purification of individual components was achieved by a combination of solvent partitions, Sephadex LH-20 exclusion, C18 bonded-phase silica gel adsorption, diol partition and liquid-liquid countercurrent chromatographies. Seven closely related components were separated and assigned structures 4, 11, 12, 13, 14, and 16 to phenelfamycins A to F respectively and structure 17 to unphenelfamycin. These structures were elucidated employing a variety of spectroscopic techniques, including extensive use of 1D and 2D NMR spectroscopy.
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  • A. D. ARGOUDELIS, L. BACZYNSKYJ, S. A. MIZSAK, F. B. SHILLIDAY
    1988 Volume 41 Issue 10 Pages 1316-1330
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    O-Demethylpaulomycin A (C33H44N2O17S), O-demethylpaulomycin B (C32H42N2O17S), paulomenol A (C29H43NO16), paulomenol B (C28H41NO16), and the hydrogen sulfide adducts of paulomycin A (U-77, 802, C34H48N2O17S2), and paulomycin B (U-77, 803, C33H46N2O17S2) have been isolated from fermentations of Streptomyces paulus strain 273. The structure of these compounds was determined by 1H and 13C NMR and fast atom bombardment mass spectrum spectroscopic techniques and degradative studies. The antibacterial properties of these new metabolites, which are related to paulomycins A and B (J. Antibiotics 35: 285-294, 1982), are briefly discussed.
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  • I. PRODUCTION, ISOLATION, CHEMICAL PROPERTIES AND BIOLOGICAL ACTIVITY
    MASAHISA OKA, YUJI NISHIYAMA, SHINICHI OHTA, HIDEO KAMEI, MASATAKA KON ...
    1988 Volume 41 Issue 10 Pages 1331-1337
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    New antitumor antibiotic glidobactins A, B and C were isolated from the cultured broth of a gliding bacterium, Polyangium brachyspomm sp. nov. No. K481-B101. They are novel molecules carrying the common cyclic tripeptide nucleus substituted with different α, β, Υ, -δ-unsaturated fatty acids. Glidobactins exhibit broad inhibitory activity against fungi and yeasts, and prolong the life span of mice inoculated with P388 leukemia cells.
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  • II. STRUCTURE ELUCIDATION
    MASAHISA OKA, KAZUKO YAGINUMA, KEIICHI NUMATA, MASATAKA KONISHI, TOSHI ...
    1988 Volume 41 Issue 10 Pages 1338-1350
    Published: October 25, 1988
    Released: April 19, 2006
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    The structures of new antitumor antibiotics, glidobactins A (Ia), B (Ib) and C (Ic) were elucidated by a combination of chemical and enzymatic degradations and spectral analyses. They have in common a cyclized tripeptide nucleus composed of L-threonine, 4(S)-amino-2(E)pentenoic acid and erythro-4-hydroxy-L-lysine, and differ from each other in the unsaturated fatty acid moiety attached to the peptide.
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  • KEI-ICHI NUMATA, MASAHISA OKA, YASUKAZU NAKAKITA, TSUTOMU MURAKAMI, TA ...
    1988 Volume 41 Issue 10 Pages 1351-1357
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Glidobactin deacylating activity was found in a bacterial strain of Pseudomonas sp. Glidobactamine, a key intermediate for acyl analogues of glidobactin, was isolated from the enzymatic degradation products of glidobactins after treatment using a column of fibrous active gel on which the cells of the Pseudomonas strain were immobilized. The chemical structure of glidobactamine was confirmed as the intact peptide moiety of glidobactins by chemical reformation of glidobactin A from glidobactamine and 2, 4-dodecadienoic acid which is the constitutive fatty acid of glidobactin A.
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  • KEI-ICHI NUMATA, TSUTOMU MURAKAMI, MASAHISA OKA, HARUAKI YAMAMOTO, MAS ...
    1988 Volume 41 Issue 10 Pages 1358-1365
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Polyangium brachysporum sp. nov. strain ATCC 53080 produces a novel type of antifungal and antitumor antibiotic complex, glidobactins A, B and C. Enhanced production of minor components, glidobactins B and C, was achieved by medium modification. The addition of soybean oil or corn oil, which are rich in unsaturated C18 fatty acids, to the fermentation medium led to an increased production of components B and C. Productivity of component C was selectively enhanced by the addition of oleic acid-rich oils, olive oil and Tween 80 (polyoxyethylene sorbitan mono-oleate). Furthermore, precursing palmitoleate, linoleate and oleate permitted the direct biosynthesis of components A, B and C, respectively. The fermentation with 3% addition of an appropriate oil at initial time provided an optimal production of component B or C.
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  • MITSUAKI TSUNAKAWA, HIDEO KAMEI, MASATAKA KONISHI, TAKEO MIYAKI, TOSHI ...
    1988 Volume 41 Issue 10 Pages 1366-1373
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A new antitumor antibiotic porothramycin was produced by a new strain of Streptomyces albus1, 2). The antibiotic was isolated in two active forms, the natural free hydroxyl form (porothramycin A) or the crystalline methyl ether form (porothramycin B) depending upon the isolation process used. Structural studies established that porothramycin is a new member of the pyrrolo[1, 4]benzodiazepine group antibiotics having only one substituent on the benzene ring. The antibiotic exhibited antimicrobial activity against Gram-positive bacteria and anaerobes and significantly prolonged the survival times of mice implanted with experimental tumors.
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  • I. 7-[2-(2-AMINOTHIAZOL-4-YL)-2-(Z)-OXYIMINOACETAMIDO]-3-[(SUBSTITUTED-1-PYRIDINIO)METHYL]-CEPH-3-EM-4-CARBOXYLATES
    RUDOLF LATTRELL, JÜRGEN BLUMBACH, WALTER DUERCKHEIMER, HANS-WOLFR ...
    1988 Volume 41 Issue 10 Pages 1374-1394
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    7-[2-(2-Aminothiazol-4-yl)-2-(Z)-oxyiminoacetamido]-3-[(substituted-1-pyridinio)methyl]ceph-3-em-4-carboxylates II are a group of β-lactam antibiotics with extraordinary high antibacterial activity. The promising member of this group, cefpirome (HR 810, II-1) is a candidate for clinical use. Synthetic pathways to II starting from cefotaxime derivatives I or 7-aminocephalosporanic acid (7-ACA) are described. A preferred method for the conversion of I to II or 7-ACA to precursors III respectively employs iodotrimethylsilane and an excess of the pyridine base. Structure-activity studies reveal an optimum overall activity in the series of pyridines with fused saturated and unsaturated rings or cyclopropyl- and alkoxy substituents. Favorable oxyimino substituents are methyl, ethyl, difluoromethyl and carbamoylmethyl groups. Acidic substituents lead to decreased activity against Staphylococcus aureus SG 5.11. Introduction of halogen in the thiazole nucleus causes improvement of activity against the K1 β-lactamase producing Klebsiella aerogenes 1082 E strain.
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  • II. ANALOGUES OF CEFPIROME WITH DIFFERENT 7-HETEROARYLACETAMIDO AND 3'-AMMONIUM SUBSTITUENTS
    RUDOLF LATTRELL, JÜRGEN BLUMBACH, WALTER DUERCKHEIMER, KLAUS FLEI ...
    1988 Volume 41 Issue 10 Pages 1395-1408
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis and antibacterial activity in vitro of 7-(2-heteroarylacetamido)-3-[(2, 3-cyclopentenopyridinium)methyl]cephalosporins and of some related compounds with different ammonium functions in 3'-position are described. The 7-[5-amino-1, 2, 4-thiadiazol-3-yl] and the 7-[4-aminopyrimidin-2-yl] analogues of cefpirome and compounds with 3-aliphatic ammoniummethyl functions have excellent antibacterial activity. Cephalosporins with different N-heterocycles other than pyridine in 3'-position are less active than their 3-pyridiniummethyl analogues. Attachment of a pyridinium group to a cephem at C-3 via a thiomethyl or an aminomethyl bridge causes reduction of antibacterial activity.
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  • III. 7α-METHOXY AND 7α-FORMAMIDO ANALOGUES OF CEFPIROME
    RUDOLF LATTRELL, WALTER DUERCKHEIMER, MICHAEL LIMBERT
    1988 Volume 41 Issue 10 Pages 1409-1417
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    7α-Methoxy and 7α-formamido derivatives of cefpirome (HR 810) have been synthesized and tested in comparison with cefpirome and some analogues 1 against aerobic and anaerobic bacteria. Cefpirome and analogues 1 have good activity against Gram-positive and only limited activity against Gram-negative anaerobic bacteria. 7α-Methoxy derivatives 2 show only a slight improvement of activity against Gram-negative anaerobes and are less active against all aerobes. Introduction of the 7α-formamido group (compounds 3) results in an overall loss of activity towards both aerobic and anaerobic bacteria.
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  • 1. THE SYNTHESIS OF SOME 3-SUBSTITUTED N-AZAMONOBACTAM DERIVATIVES
    WILLIAM V. CURRAN, ADMA A. Ross, VING J. LEE
    1988 Volume 41 Issue 10 Pages 1418-1429
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Ring closure of the N-(tert-butyloxycarbonyl)-L-serine 2-(diphenylmethylene)hydrazide (10a) and the corresponding L-threonine derivative (10b) gave good yields of the β-lactams 11a and 11b. Catalytic hydrogenation afforded the corresponding N-ammo β-lactams 12a and 12b. These compounds were then further transformed into 3-(S)-[[(2-amino-4-thiazolyl)-(Z)-(methoxyimino)acetyl]amino-2-oxo-1-azetidinyl]sulfamic acid analogs 18, 23, and 30a and 30b. None of these compounds exhibited any interesting biological activity.
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  • R. NAGARAJAN, A. A. SCHABEL, J. L. OCCOLOWITZ, F. T. COUNTER, J. L. OT ...
    1988 Volume 41 Issue 10 Pages 1430-1438
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Several glycopeptides containing N-acyl groups have been isolated recently. We undertook the synthesis of N-acyl vancomycins, using the active ester method. The in vitro and in vivo antibacterial activity were evaluated, and structure-activity relationship of this series of semisynthetic vancomycins is discussed.
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  • IV. THE SYNTHESIS OF 3'-AMINOMETHYLDIHYDROSPECTINO-MYCINS VIA SPECTINOMYCIN 3'-CYANOHYDRINS
    RICHARD C. THOMAS, EDWARD L. FRITZEN
    1988 Volume 41 Issue 10 Pages 1439-1444
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The C-3'-carbonyl group of N-protected spectinomycin is converted into the corresponding aminomethylalcohols via the intermediacy of cyanohydrins. Methodology for the selective synthesis of either epimer with retention of protection in the aminocyclitol ring provides valuable synthetic intermediates for the preparation of analogs of this important antibiotic. The new methodology provides an efficient synthesis of the highly active 3'-aminomethyldihydrospectinomycins.
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  • V. THE SYNTHESIS AND BIOLOGICAL ACTIVITY OF SPECTINOMYCIN ANALOGS WITH RING-EXPANDED SUGARS
    RICHARD C. THOMAS, EDWARD L. FRITZEN
    1988 Volume 41 Issue 10 Pages 1445-1451
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Tiffeneau-Demjanov rearrangement of 3'(R)-N, N'-dibenzyloxycarbonyl-3'-aminomethyldihydrospectinomycin results in ring expansion affording the homologous analog with a sevenmembered sugar ring. In stark constrast, attempted rearrangement of the 3'-S-isomer leads only to epoxide formation. Deprotection of the ring-expanded homolog gives homospectinomycin. The synthesis and biological activity of this interesting new member of the spectinomycin series and the derived dihydrohomospectinomycin is detailed in this paper.
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  • Y. YAGI, L. BACZYNSKYJ, S. A. MIZSAK, A. D. ARGOUDELIS
    1988 Volume 41 Issue 10 Pages 1452-1461
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Employing osmotically shocked lysate of a spectinomycin resistant strain of Escherichia coli, trospectomycin, a new alkylspectinomycin, was adenylylated in the presence of adenosine 5'-triphosphate and magnesium ion. A highly resistant strain of E. coli was obtained by transforming a laboratory strain with a newly constructed plasmid consisting of pBR322 and a determinant for spectinomycin resistance originally found on a low copy number plasmid in E. coli strain NR79. The biologically inactive adenylylated trospectomycin was found to be trospectomycin 6-(5'-adenylate).
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  • MAKOTO HORI, NOBUO SAKATA, YASUHIRO NIINO, OSAMU MAKABE, MASA HAMADA, ...
    1988 Volume 41 Issue 10 Pages 1462-1470
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A mixed probe consisting of two synthetic deoxynucleotides (52 and 54 mers referred to as 50-mer) with arbitrarily chosen C or G for the third letters was prepared based on the amino acid sequences No. 31 -48 and No. 72-90 of macromomycin (MCM) apoprotein and successfully used to clone the MCM apoprotein gene. Digestion with Sph I of total DNA of MCM-producing Streptomyces macromomyceticus M480-M1 yielded a 2.6-kb fragment that hybridized strongly to the probes. The hybridized probe was stable to washing with 3×SSC at 75°C. Radioactivity derived from the hybridized probe was comparable to that expected theoretically from hybridization between the probe and the true target sequence. The 2.6-kb fragment was cloned into Escherichia coli RR1 with pBR322 and subsequently subcloned into Streptomyces lividans TK21 with pIJ702. Nucleotide sequence analysis of the cloned fragment verified the exsistence of the sequence corresponding to the amino acid sequence of MCM apoprotein and about 90% homologies with the probes. Thus, the use of relatively long deoxynucleotide probes with arbitrarily chosen C or G for the third letters will be advantageous in cloning Streptomyces protein genes where more than 90% of the third letters have been known to be C or G. In addition, theoretical diagnosis of hybridization should be a great help to distinguish true positives from false ones.
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  • II. DEPENDENCE ON PUTATIVE QUINONE POCKET ON THE ENZYME MOLECULE
    YUKIO HAFURI, ERIKO TAKEMORI, KEIKO OOGOSE, YOSHIO INOUYE, SHOSHIRO NA ...
    1988 Volume 41 Issue 10 Pages 1471-1478
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Inhibition of avian myeloblastosis virus (AMV) reverse transcriptase by natural and synthetic quinones including antibiotics could be accounted for by an oxidation-reduction reaction. The quinones were shown to function as electron acceptors as revealed by the catalytic oxidation of NADH by Clostridium kluyveri diaphorase which was in excellent agreement with enzyme inhibition activity.
    The kinetics of inhibition of AMV reverse transcriptase by three synthetic quinones with different core structures, i.e., 6-methoxy-5, 8-dihydroquinoline-5, 8-dione, 5, 8-dihydroisoquinoline-5, 8-dione and 1, 4-naphthoqumone, were studied. These quinones inhibited reverse transcriptase in the same manner as streptonigrin (STN) and were shown to act at a single class of reaction site(s) on the enzyme molecule. In contrast, the quinones with bulky substituents, i.e., 7-(2-nitrophenethylamino)-5, 8-dihydroisoquinoline-5, 8-dione and 7-methoxy6-methyl-3-piperidino-5, 8-dihydroisoquinoline-5, 8-dione, were inactive as inhibitors of reverse transcriptase, whereas they retained competent catalytic activities in the oxidation of NADH by C. kluyveri diaphorase. Based on these observations, the existence of a specific site of interaction on the enzyme molecule, referred to as a quinone pocket, was proposed. The quinone pocket might play a crucial role in the early sequence of events leading to the inhibition of reverse transcriptase by quinones including STN and sakyomicin A (SKM). Access of SKM to a quinone pocket might be restricted due to its bulky structure in the vicinity of the quinone group. This is inferred from unsuccessful inhibition of reverse transcriptase by the quinones with bulky substituents, resulting in much poorer inhibition of reverse transcriptase in spite of more potent electron acceptor activity in the oxidationreduction system as compared with those of STN.
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  • YOSHIKO YOKOTA, YOSHIMI WAKAI, YUJI WATANABE, YASUHIRO MINE
    1988 Volume 41 Issue 10 Pages 1479-1487
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The effects of route and starting time of administration on FK-565 inhibition of splenomegaly by Friend leukemia virus (FLY) were studied in mice, and the concomitant effect of FK-565 in allowing reduction of zidovudine dosage was estimated.
    FK-565 inhibited splenomegaly in intravenous and oral doses of 0.01 to 1 mg/kg, but time of initial dosing had little effect on this inhibition. When 0.01 or 1 mg/kg of FK-565 was given intravenously with mtraperitoneal doses of 0.63, 2.5, 10 and 40m g/kg of zidovudine, the inhibition rate of splenomegaly at all doses was markedly and dose-dependently higher than when either drug was given alone, and the concomitant use of FK-565 with zidovudine enabled a 16-fold reduction of the dose of zidovudine. The survival rate and survival time after infection with massive amounts of FLV were higher when FK-565 1 mg/kg and zidovudine 20 mg/kg were given in combination than when either drug was given alone. Inhibition of FLV splenomegaly was reflected in the prolonged survival time of the infected mice.
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  • YUKIHIKO KAMEDA, NAOKI ASANO, KATSUHIKO MATSUI, SATOSHI HORII, HIROSHI ...
    1988 Volume 41 Issue 10 Pages 1488-1492
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • HIROKO OGINO, KATSUYOSHI IWAMATSU, TOMOKO SHOMURA, WILLIAM E. HULL, TA ...
    1988 Volume 41 Issue 10 Pages 1493-1496
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • KIKUO MASUDA, TAKAAKI NAKAMURA, KYOICHI SHIMOMURA, TOSHIHIRO SHIBATA, ...
    1988 Volume 41 Issue 10 Pages 1497-1499
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • HIROSHI YAMAKI, TOSHIO NISHIMURA, KEITA MATSUNAGA, HIDEO SUZUKI, HIDEY ...
    1988 Volume 41 Issue 10 Pages 1500-1502
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • JUNPEI ITOH, TOMIO TAKEUCHI, SEIICHI SUZUKI, HIROSHI AMEMIYA
    1988 Volume 41 Issue 10 Pages 1503-1505
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • NAOKI TSUJI, TOSHIYUKI KAMIGAUCHI, MASAAKI KOBAYASHI, YOSHIHIRO TERUI
    1988 Volume 41 Issue 10 Pages 1506-1510
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • G. T. CARTER, D. W. PHILLIPSON, J. J. GOODMAN, T. S. DUNNE, D. B. BORD ...
    1988 Volume 41 Issue 10 Pages 1511-1514
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • KAZUNORI OHBA, HIRO-OMI WATABE, TORU SASAKI, YASUO TAKEUCHI, YOSHIO KO ...
    1988 Volume 41 Issue 10 Pages 1515-1519
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • KUNIAKI TATSUTA, YOSHIYUKI KOBAYASHI, HIROKI GUNJI
    1988 Volume 41 Issue 10 Pages 1520-1523
    Published: October 25, 1988
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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