The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 47 , Issue 12
Showing 1-28 articles out of 28 articles from the selected issue
  • TAKASHI FUJITA, HIROSHI HATANAKA, KEN-ICHI HAYASHI, NOBUHARU SHIGEMATS ...
    1994 Volume 47 Issue 12 Pages 1359-1364
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A novel human leukocyte elastase (HLE) inhibitor, FR901451 was discovered in the fermentation broth of a bacteria. The bacteria was identified as Flexibacter sp. No. 758. FR901451 has a molecular weight of 1269 and a molecular formula of C60H79N13O18. The mode of inhibition against HLE is competitive, with a Ki value of 9.8×10-9 M.
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  • TAKASHI FUJITA, YASUHIKO SHINGUH, AKIKO YAMAZAKI, KUNIO NAKAHARA, MASA ...
    1994 Volume 47 Issue 12 Pages 1365-1368
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Intratracheal (i.t.) or intravenous (i.v.) administration of FR901451, a potent inhibitor of human leukocyte elastase (HLE) prevented HLE-induced lung hemorrhage in hamsters with ED50 values of 10.5μg/site and 8.1mg/kg, respectively. αl-Antitrypsin (αl-AT) also showed inhibitory effect in this model. However, the ED50 value by i.t. injection of FR901451was 20-fold lower than that of αl-AT. Moreover, FR901451 i.t. significantly modulated porcine pancreas elastase (PPE)-induced changes of the respiratory mechanics in hamsters. The ED50 values were 529μ/site and 244μ/site, which were expressed by static lung compliance (Cst) and vital capacity (VC) of the lungs, respectively. These results suggest that FR901451 could be clinically useful agent for the treatment of the destructive lung disease such as pulmonary emphysema.
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  • MASAE MUTOH, NAOKI NAKADA, SHOKO MATSUKUMA, SHOICHI OHSHIMA, KIYOSHI Y ...
    1994 Volume 47 Issue 12 Pages 1369-1375
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Panclicins A, B, C, D, and E are novel pancreatic lipase inhibitors isolated from Streptomyces sp. NR 0619. Structurally, panclicins A, B, C, D, and E are analogues of tetrahydrolipstatin (THL), which contains β-lactone and a N-formyl leucine ester, and the IC50s of panclicins A, B, C, D, and E for porcine pancreatic lipase are 2.9, 2.6, 0.62, 0.66, and 0.89μ, respectively. The potency of the inhibitory activity of each compound is attributed to the amino acid moiety of each structure. The panclicins are either glycine-type compounds such as panclicins C, D, E, which are two to threefold more potent than THL, or they are alanine-type compounds such as panclicins A and B, which are less potent than the glycine compounds. The inhibitory profiles of the panclicins for other lipases such as post-heparin plasma lipases and bacterial lipases are similar to those for pancreatic lipase. Panclicins A, B, C, D, and E, in a manner similar to THL, irreversibly inhibit pancreatic lipase. However, the compounds don't irreversibly inhibit the enzyme as strongly as THL does.
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  • KLYOSHI YOSHINARI, MASAHIRO AOKI, TATSUO OHTSUKA, NOBORU NAKAYAMA, YOS ...
    1994 Volume 47 Issue 12 Pages 1376-1384
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Panclicins A-E are novel and potent pancreatic lipase inhibitors produced by Streptomyces sp. NR 0619. Their structures have been elucidated based on NMR and FAB-MS experiments. The relative configurations have also been determined by NMR experiments. The absolute stereochemistry has been determined by the chiral HPLC analysis of the hydrolysates of panclicins A and B and by modified Mosher's method on a derivative of panclicin A. They are structurally related to β-lactone esterase inhibitors of microbial origin, lipstatin, valilactone, ebelactones and esterastin. Panclicins also contain a β-lactone structure with two alkyl chains, one of which has an N-formylalanyloxy or N-formylglycyloxy substituent.
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  • SHUICHI GOMI, SHOICHI AMANO, ERIKO SATO, SHINJI MIYADOH, YOSHIO KODAMA
    1994 Volume 47 Issue 12 Pages 1385-1394
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Three new antibiotics SF2738A, B and C, and their analogs were isolated from the culture broth of Streptomyces sp. The antibiotics are active against Gram-positive bacteria, Gram-negative bacteria and fungi, and exhibited cytotoxic activity against P388 murine leukemia cells with IC50 values of 0.08, 0.25 and 7.5 μg/ml, respectively. Their structures were determined by spectral analyses and chemical conversion. Especially, the structure of SF2738A was confirmed to be (E)-((4-methoxy-5-methylthio-2-(2-pyridyl)pyridin-6-yl)methylene)azanol by X-ray crystallographic analysis.
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  • MITSUKO SEKI-ASANO, TADAYASU OKAZAKI, MICHIO YAMAGISHI, NORIYOSHI SAKA ...
    1994 Volume 47 Issue 12 Pages 1395-1401
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    During the course of our screening program for natural product drugs effective against multidrug resistant cells by using adriamycin resistant HL-60 cells, we have discovered a new 12 membered macrolide FD-895 in the fermentation broth of Streptomyces hygroscopicus A-9561 isolated from a soil sample collected at Iriomote Island, Okinawa prefecture, Japan. FD-895 showed stronger cytocidal activities against in vitro tumor cell lines than adriamycin. FD-895 had the same IC50 values against parent and adriamycin resistant HL-60 cells.
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  • CHUL-HOON LEE, SUNGHO KIM, BONGCHUL HYUN, JUNG-WOO SUH, CHANGSUEK YON, ...
    1994 Volume 47 Issue 12 Pages 1402-1405
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Cepacidine A is a potent antifungal antibiotic produced by Pseudomonas cepacia AF 2001. The compound was isolated from the fermentation broth with 1 vol isopropyl alcohol, followed by the collection of the precipitation formed upon concentration of the extract. Purification was effected by chromatography on Diaion HP-20, alumina and reversed phase C18 followed by TLC on silica gel. These techniques afforded the two closely related compounds, cepacidine A1 and cepacidine A2. A mixture of these two compounds called cepacidine A, showed high in vitro antifungal activity against the various animal and plant pathogenic fungi. The activity was diminished by the presence of serum. No antibacterial activity was demonstrable.
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  • YOONGHO LIM, JUNG-WOO SUH, SUNGHO KIM, BONGCHUL HYUN, CHOONGSUP KIM, C ...
    1994 Volume 47 Issue 12 Pages 1406-1416
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Cepacidine A is a novel glycopeptide with a potent antifungal activity, which is produced by Pseudomonas cepacia AF 2001. Its molecular weight was determined by FAB-MS (m/z 1215). The compound is comprised of glycine (1), serine (2), 2, 4-diaminobutyric acid (1), aspartic acid (1), β-hydroxy tyrosine (1), βMiydroxy asparagine (1), xylose (1) and 5, 7-dihydroxy-3, 9-diamino-octadecanoic acid (1). Unfortunately, cepacidine A is a mixture of A1 and A2, either of which is barely distinguishable. Cepacidine A2 includes asparagine (1) instead of β-hydroxy asparagine (1) of cepacidine A1 The MS data and the NOESY, TOCSY and HMBC spectra show that cepacidine A is a cyclic peptide and xylose is connected to 5, 7-dihydroxy-3, 9-diaminooctadecanoic acid.
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  • VERNAN S. BERNAN, DEBORAH A. MONTENEGRO, JOSEPH D. KORSHALLA, WILLIAM ...
    1994 Volume 47 Issue 12 Pages 1417-1424
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    An actinomycete strain designated LL-31F508 was isolated from an intertidal sediment sample collected in Key West, Florida. Culture LL-31F508 was assigned to the Streptomyces genus based on the presence of LL-diaminopimelic acid (DAP) in the cell wall and observations of spiny spores using scanning electron microscopy (SEM). Excellent antimicrobial activity against Staphyloccoccus and Enterococcus spp. were detected in both the supernatant and cell extract samples from fermentations of culture LL-31F508. Production of antibiotic activity peaked at 48-50 hours and closely paralleled cell growth, during which time glucose was more rapidly assimilated than dextrin. A series of new antibiotics called the bioxalomycins was identified as the antibacterial products from fermentations of this culture. Fermentation conditions for production of bioxalomycin α differed substantially from those required for production of a related compound, naphthyridinomycin, by the reference culture Streptomyces lusitanus NRRL 8034.
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  • ANDREW L. STALEY, KENNETH L. RINEHART
    1994 Volume 47 Issue 12 Pages 1425-1433
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Three new tetrahydroanthracene antibiotics have been isolated from modified culture broths of Streptomyces spectabilis. The new compounds, spectomycins Al, A2 and Bl, exist as monomeric (C20H20O7, Al; C19H18O7, A2) and as symmetrical dimeric (C38H34O14; Bl) forms. Only spectomycin Bl has moderate activity against Gram-positive microorganisms. We report here the structure elucidation and biosynthetic origin of these compounds.
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  • VALERIE S. BERNAN, DEBORAH A. MONTEREGRO, JOSEPH J. GOODMAN, MAHENDER ...
    1994 Volume 47 Issue 12 Pages 1434-1441
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Actinomycete culture LL-D37187 has been found to produce the new polyether antibiotic martinomycin1). Taxonomic studies, including morphological, physiological, and cell wall chemistry analyses, revealed that culture LL-D37187 is a novel streptomycete species, and the proposed name is Streptomyces salvialis. Martinomycin exhibits activity against the Southern Army Worm (Spodoptera eridania) and Gram-positive bacteria.
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  • ANA-MARIA OBREGON, LAURA ESCALANTE, RIAN GONZALEZ, ROMAIA RODRIGUEZ, S ...
    1994 Volume 47 Issue 12 Pages 1442-1446
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The effect of inorganic phosphate on the fermentative production of gentamicin by Micromonospora purpurea has been studied using a chemically denned medium. Phosphate concentrations higher than 5.75 mM (lg/liter-1) did not inhibit growth but specifically prevented antibiotic formation. Changes in the pH medium and carbon or nitrogen depletion were excluded as the cause of antibiotic underproduction. The use of a phosphate analogue, a protein synthesis inhibitor and the profiles of differential rate of antibiotic production suggested that phosphate itself transiently repressed gentamicin formation. Phosphate affected the formation of 2-deoxystreptamine from 2-deoxyinosose, a none phosphorylated substrate.
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  • HARUYASU KINASHI, EUIRO MORI, AKIRA HATANI, OSAMU NIMI
    1994 Volume 47 Issue 12 Pages 1447-1455
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Streptomyces rochei 7434AN4, a producer of lankacidin and lankamycin contains three large linear plasmids, pSLA2-L (200 kb), M (100 kb), and S (17 kb). Studies on the mutants of 7434AN4 having a different plasmid profile showed a parallel relationship between the presence of pSLA2-L and the production of both lankacidin and lankamycin. When pSLA2-L was transferred by protoplast fusion to S. rochei2-39, a non-antibiotic-producing mutant of 7434AN4 which contained no detectable plasmid, the fusants gained the capacity to produce both antibiotics. From the physical maps of pSLA2-L and pSLA2-Ll, a deletion plasmid (160 kb) of pSLA2-L, the latter plasmid was determined to contain a symmetrical linear repeat composed of the right 80-kb part of pSLA2-L. Four other lankacidin-producing Streptomyces strains were also found to have distinctive large linear plasmids which hybridized with the pSLA2-L probe. These results support the involvement of pSLA2-L in the production of lankacidin and lankamycin in S. rochei 7434AN4.
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  • ERIK S. ADAMS, KENNETH L. RINEHART
    1994 Volume 47 Issue 12 Pages 1456-1465
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A new pactamycin analogue, 5"-fluoropactamycin, was prepared by directed biosynthesis. Supplementation of the fermentation medium of Streptomyces pactum, var. pactum with 3-amino-5-fluorobenzoic acid, an analogue of 3-aminobenzoic acid, an advanced precursor in pactamycin biosynthesis, resulted in co-production of pactamycin and the new pactamycin analogue. A similar feeding experiment with 3-amino-5-methylbenzoic acid did not result in formation of the corresponding methylated pactamycin analogue, but only in inhibition of pactamycin production. Comparison of antimicrobial and cytotoxic activities of pactamycin and 5"-fluoropactamycin showed no significant differences.
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  • RAYMOND C. M. LAU, KENNETH L. RINEHART
    1994 Volume 47 Issue 12 Pages 1466-1472
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Berninamycins B, C, and D were isolated from fermentation of Streptomyces bernensis and their structures were studied with 13C NMR and FAB mass spectrometry. Berninamycin B has a valine unit in its cyclic peptide loop instead of the β-hydroxyvaline unit found in berninamycin A. Berninamycin D has two fewer dehydroalanine units attached to the carboxyl carbon of the pyridine ring. Based on FAB-MS results, berninamycin C is postulated to have only one dehydroalanine unit attached to the carboxyl carbon of pyridine. The biogenesis of berninamycins B, C, and D is discussed.
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  • HIDEYUKI HARUYAMA, YOSHIKO OHKUMA, HIDEMI NAGAKI, TAKESHI OGITA, KAZUH ...
    1994 Volume 47 Issue 12 Pages 1473-1480
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structures of matlystatins, novel type IV collagenase inhibitors isolated from Actinomadura atramentaria, have been determined by a systematic application of homo- and heteronuclear 2D NMR and FAB-MS/MS techniques. Their structures were characterized by the presence of piperazic acid and hydroxamic acid moieties, structural motifs often seen in protease inhibitors.
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  • KAZUHIKO TAMAKI, SHINWA KURIHARA, TETSUO OIKAWA, KAZUHIKO TANZAWA, YUK ...
    1994 Volume 47 Issue 12 Pages 1481-1492
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The first total synthesis of matlystatin B (1a), a low molecular weight inhibitor of type IV collagenases, was accomplished, and its absolute configuration was unambiguously determined. Furthermore, ten stereoisomers of 1a were synthesized, and the inhibition of the 92 kDa type IV collagenase and of other metalloproteinases by each stereoisomer was investigated.
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  • ADRIANO MALABARBA, ROMEO CIABATTI, JÜRGEN KETTENRING, PIETRO FERR ...
    1994 Volume 47 Issue 12 Pages 1493-1506
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Removal, by selective reduction, of the acetylglucosamine from teicoplanin A2-2 (CTA/2) produced the 34-de(acetylglucosaminyl)-34-deoxy pseudoaglycone (II). This compound was more active in vitro than CTA/2 against coagulase-negative staphylococci (CNS).
    Amide derivatives obtained by condensation of the carboxyl group of II with primary amines were particularly active against Streptococcus pyogenes and had some in vitro activity against Van A enterococci highly resistant to both teicoplanin and vancomycin. Among them, a carboxamide (VII) with a branched tetramine also had better activity than the corresponding amide of teicoplanin against CNS. In contrast, the dimethylamide (VIII) of II had little activity against VanA enterococci.
    While the overall structure of the heptapeptide backbone of the secondary carboxamides of II is the same as in CTA/2 and its amide derivatives, in deoxy pseudoaglycone II and its tertiary amide VIII the 51, 52-peptide bond undergoes a conformational change from the original cisoid to the transoid orientation. This difference between the secondary amides of II and dimethylamide VIII is reflected in their different antibacterial spectrum.
    The direct synthesis of the amides of deoxy pseudoaglycone II from parent CTA/2-amides by reaction with sodium borohydride is also described.
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  • SHIGETO NEGI, MOTOSUKE YAMANAKA, ISAO SUGIYAMA, YUKI KOMATSU, MANABU S ...
    1994 Volume 47 Issue 12 Pages 1507-1525
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis and antibacterial activities of 7β-[2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetarnido]-3-N, N-dimethylcarbamoyloxymethyl-3-cephem-4-carboxylic acid (E1 100) and its analogs are described, as well as oral absorbability and in vivo activities of the l-(isopropoxycarbonyloxy)ethyl ester (E1 101) and its analogous esters. The introduction of acyclic and cyclic lower alkyl groups at the N-position of 3-carbamoyloxymethyl cephems influences antibacterial activities, especially against H. influenzae, and oral absorbability of their prodrug esters. The structure-activity relationships are also discussed.
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  • SHIGETO NEGI, MANABU SASHO, MOTOSUKE YAMANAKA, ISAO SUGIYAMA, YUKI KOM ...
    1994 Volume 47 Issue 12 Pages 1526-1540
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    In an effort to find a new oral cephalosporin with well-balanced antibacterial spectrum, good oral absorbability and long plasma half-life, a series of oxyimino aminothiazolyl 3-[(E)- or (Z)-N-substituted carbamoyloxy]propenyl cephems was synthesized and evaluated for antibacterial activity and oral absorbability. The substituents of the carbamoyloxy group affected their in vitro activity and bioavailability after oral administration of their pivaloyloxymethyl esters at the C-4 position. The compound possessing an N, N-dimethylcarbamoyloxy moiety at the C-3 position showed good oral absorption and well-balanced antibacterial activity. In this report, the structure-activity relationships and the structure-oral absorbability relationships of 3-(N-substituted carbamoyloxy)-propenyl cephems are described.
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  • BONG-SIK YUN, TOMOMI HIDAKA, KAZUO FURIHATA, HARUO SETO
    1994 Volume 47 Issue 12 Pages 1541-1545
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • TOMIO MORINO, MASAKAZU NISHIMOTO, NORIKO ITOU, TAKAAKI NISHIKIORI
    1994 Volume 47 Issue 12 Pages 1546-1548
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • GUY. T. CARTER, GERHARD SCHLINGMANN, GRANT B. KENION, LISA MILNE, MAHE ...
    1994 Volume 47 Issue 12 Pages 1549-1553
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • TAKASHI NISHIKAWA, SATOMI SUZUKI, HIDEKI OHTANI
    1994 Volume 47 Issue 12 Pages 1554-1556
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • TOM S. CHEN, B. PETUCH, R. WHITE, G. DEZENY, X. Li, B. ARISON, T. BEAT ...
    1994 Volume 47 Issue 12 Pages 1557-1559
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • OLA BERGENDORFF, HEIDRUN ANKE, KIM DEKERMENDJIAN, MOGENS NIELSENT, SHA ...
    1994 Volume 47 Issue 12 Pages 1560-1561
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • JUN KAWASHIMA, FUMI ITO, TAKASHI KATO, MITSURU NIWANO, HIROYUKI KOSHIN ...
    1994 Volume 47 Issue 12 Pages 1562-1563
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • PAOLO TAVECCHIA, PATRIZIA GENTILI, MICHAEL KURZ, CRISTINA SOTTANI, RIC ...
    1994 Volume 47 Issue 12 Pages 1564-1567
    Published: December 25, 1994
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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