The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 44 , Issue 3
Showing 1-16 articles out of 16 articles from the selected issue
  • I. TAXONOMY, FERMENTATION, ISOLATION AND PHYSICO-CHEMICAL PROPERTIES
    MICHIKO TAKEUCHI, RYUZO ENOKITA, TAKAO OKAZAKI, TAKESHI KAGASAKI, MASA ...
    1991 Volume 44 Issue 3 Pages 263-270
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A strain of actinomycetes identified as Pseudonocardia compacta subsp. helvetica produced new glycopeptide antibiotics, helvecardins A and B. They were isolated from culture broth mainly by affinity chromatography of D-alanyl-D-alanine and preparative HPLC. The physico-chemical properties of helvecardins A and B showed that they resemble each other. Though helvecardin A was structurally related to β-avoparcin, it clearly differed in the presence of an O-methyl moiety in its NMR spectrum.
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  • II. STRUCTURAL ELUCIDATION
    MICHIKO TAKEUCHI, SHUJI TAKAHASHI, MASATOSHI INUKAI, TAKEMICHI NAKAMUR ...
    1991 Volume 44 Issue 3 Pages 271-277
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Helvecardins A and B, which are produced by Pseudonocardia compacta subsp. helvetica, are new members of glycopeptide antibiotics. They contain the same pseudoaglycone as β-avoparcin and the same compositions of neutral sugar, amino sugar, and amino acid except that 2'-O-methylrhamnose was detected in helvecardins instead of rhamnose in β-avoparcin, and mannose was not detected in helvecardin B. From these results and 1H NMR and mass spectral analyses, helvecardins A and B were determined β-avoparcin 2'-O-methylated on rhamnose and deman-nosylhelvecardin A, respectively.
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  • III. BIOLOGICAL PROPERTIES
    MICHIKO TAKEUCHI, TOSHIAKI KATAYAMA, MASATOSHI INUKAI
    1991 Volume 44 Issue 3 Pages 278-281
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Helvecardins (HVCs) A and B were strongly active against aerobic and anaerobic Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA), but they were inactive against Gram-negative bacteria and fungi. Though HVC A showed only slightly stronger antimicrobial activity than β-avoparcin (AVP), its in vivo protective activity against S. aureus infection in mice was greatly superior to AVP.
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  • I. TAXONOMY, FERMENTATION, ISOLATION AND BIOLOGICAL ACTIVITY
    YOICHI HAYAKAWA, NAOYUKI KANAMARU, AKIRA SHIMAZU, HARUO SETO
    1991 Volume 44 Issue 3 Pages 282-287
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A novel antibiotic, designated lydicamycin, was isolated from the fermentation broth of an actinomycete strain identified as Streptomyces lydicus. Lydicamycin was active against Gram-positive bacteria and a certain yeast, but inactive against Gram-negative bacteria.
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  • II. PHYSICO-CHEMICAL PROPERTIES AND STRUCTURE ELUCIDATION
    YOICHI HAYAKAWA, NAOYUKI KANAMARU, NAOKO MORISAKI, KAZUO FURIHATA, HAR ...
    1991 Volume 44 Issue 3 Pages 288-292
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structure of a new antibiotic designated lydicamycin was elucidated as shown in Fig. 1 by NMR spectral analysis including a variety of 2D techniques. Lydicamycin possesses a novel skeleton contanining tetramic acid and amidinopyrrolidine moieties.
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  • MUTSUO NAKAJIMA, KAZUKO ITOI, YASUYUKI TAKAMATSU, TAKESHI KINOSHITA, T ...
    1991 Volume 44 Issue 3 Pages 293-300
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Hydantocidin, a new compound with potent non-selective herbicidal activity, was found in a submerged culture of Streptomyces hygroscopicus SANK 63584. It was isolated from the culture filtrate by the following successive treatments comprised of activated carbon, Diaion HP-20, Dowex 50WX4, and Avicel column chromatographies. Finally it was crystallized as colorless needles from acetone.
    The molecular formula, C7H10N2O6, was determined by analyses of HRFAB mass spectrum in conjunction with 13C NMR spectrometry. The structural elucidation revealed that it has a unique structure with a spiro-bond between ribose and hydantoin moieties in the molecule. The characteristic herbicidal activities against annuals as well as perennials, including monocotyledonous and dicotyledonous weeds, were observed.
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  • MASAJI KASAI, MOTOMICHI KONO, KUNIKATSU SHIRAHATA
    1991 Volume 44 Issue 3 Pages 301-308
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The first example of C-3 alkoxylation in mitomycins has been achieved. 3α-iso-Propoxy-10-O-decarbamoylmitomycin D (4) and 3α-iso-propoxymitomycin D (5) were derived from mitomycin D (3) under decarbamoylation conditions with iso-propoxide. Under similar conditions 3α-iso-propoxy-10-O-decarbamoylporfiromycin (8) and 3α-methoxy-10-O-decarbamoylmitomycin B (11) were also derived from porfiromycin (6) and mitomycin B (9), respectively. The mechanism of generation of these novel analogs was based on the premise that the key intermediate of hydroquinone iminium salt (14) was led through the iminium salt (13), followed by alkoxide addition and oxidation.
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  • MOTOMICHI KONO, MASAJI KASAI, KUNIKATSU SHIRAHATA, NORIAKI HIRAYAMA
    1991 Volume 44 Issue 3 Pages 309-312
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The configuration of mitiromycin (2) was first determined by NMR experiments including the NOE technique. The absolute structure of 2 was related to mitomycin B (3) because 2 was derived from 3 under basic conditions. The ketonic form 4 was presumed to be involved in the generation of 2.
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  • A STRUCTURE-ACTIVITY RELATIONSHIP STUD
    JEAN-CLAUDE GASC, SOLANGE GOUIN D'AMBRIERES, ANDRÉ LUTZ, JEAN-F ...
    1991 Volume 44 Issue 3 Pages 313-330
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The discovery of roxithromycin is the result of a rational and scientific process, based on the fact that at least one reason for erythromycin A's resorption variability after oral administration was its instability in the gastric juice. This instability is due to the reactivity of the ketone in position 9 in acidic medium and one chemical approach was to mask it by an oxime function. Both stereoisomers of this oxime were isolated. Direct O-alkylation of this oxime allowed access to various ether oxime derivatives and of the latter the E stereoisomers were more interesting than the Z ones. The choice of the nature of the oxime substitution was made according to the lipophilic or hydrophilic character of the aliphatic ether chain and these alterations were mainly carried out by introducing heteroatoms into this chain. These different derivatives were classified in 5 groups according to the chemical nature of the chain: Aliphatic, aromatic and nitrogen-, oxygen- and sulfur-containing chains. Two classes, those containing a nitrogen or an oxygen in the ether side chains, showed differential in vitro/in vivo antibiotic activities, with improved bioavailability. Some preliminary pharmacokinetic data confirmed this improvement and led to the selection of five candidates, from which roxithromycin emerged as the best compound.
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  • III. STRUCTURE-ACTIVITY RELATIONSHIPS OF THE 5-MEMBERED HETEROCYCLIC DERIVATIVES
    I. BENNETT, N. J. P. BROOM, G. BRUTON, S. CALVERT, B. P. CLARKE, K. CO ...
    1991 Volume 44 Issue 3 Pages 331-337
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Sodium (5RS)-Z-6-(heterocyclylmethylene)penem-3-carboxylates (2) are a series of extremely potent inhibitors of bacterial β-lactamases. A variety of 5-membered heteroaromatic derivatives have been prepared and structure-activity studies reveal a preferred substituent orientation.
    One of these derivatives, the 1-methyl-1, 2, 3-triazolyl compound (5m) is a more potent synergist of amoxycillin than clavulanic acid, sulbactam or tazobactam.
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  • IV. KIDNEY STABILITY, SERUM BINDING AND ADDITIONAL BIOLOGICAL EVALUATION OF RACEMIC DERIVATIVES
    ISABEL S. BENNETT, NIGEL J. P. BROOM, KENNETH COLEMAN, STEVEN COULTON, ...
    1991 Volume 44 Issue 3 Pages 338-343
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Sodium (5RS)-Z-6-(substituted methylene)penem-3-carboxylates (3) are extremely potent inhibitors of bacterial β-lactamases, but some members of this group of compounds are highly bound to human serum, while others are readily degraded by renal dehydropeptidase I enzyme. Consequently, the stability of a variety of 6-(substituted methylene)penems (3) to human kidney homogenate, their binding to human serum and their activity in a mouse infection model was investigated at an early stage, and were instrumental in the selection of the 1, 2, 3-triazolylmethylene derivatives (e.g. 3k) as a class of compounds worthy of further evaluation.
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  • KAYOKO SUZUKAKE-TSUCHIYA, YUKARI MORIYA, HIROYUKI KAWAI, MAKOTO HORI, ...
    1991 Volume 44 Issue 3 Pages 344-348
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A fermentation broth of Streptomyces sp. SIPI-A4-0044 inhibited in vitro growth of src or ras oncogene-expressed (onc+) cells more strongly than that of oncogene-unexpressed (onc-) counterparts. The active components were isolated and identified as hygrolidin family antibiotics (HGL). In mixed cultures consisting of onc+ and onc- cells, at an appropriate ratio, HGL showed selective toxicity to focus like structures of onc+ cells, leaving monolayer areas of onc- cells little damaged. HGL rapidly inhibited pinocytosis, or the influx of neutral red into the cells, at concentrations partially inhibitory to the cell growth. In contrast, HGL only slightly inhibited the influx of 2-deoxyglucose, nucleosides and leucine and the syntheses of DNA, RNA and protein even at high concentrations. Upon prolonged exposure to sublethal concentrations of HGL, onc- cells but not onc+ cells recovered pinocytotic activity and resumed growth.
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  • EDMUND W. HAFNER, BRELAND W. HOLLEY, KELVIN S. HOLDOM, S. EDWARD LEE, ...
    1991 Volume 44 Issue 3 Pages 349-356
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The eight natural avermectins produced by Streptomyces avermitilis have the carbon skeleton of either isobutyric or S-2-methylbutyric acid incorporated into their structures. A mutant of S. avermitilis has been isolated that contains no functional branched-chain 2-oxo acid dehydrogenase activity. The mutant, in contrast to its parent, is unable to grow with isoleucine, valine and leucine as carbon sources. In medium lacking both S(+)-2-methylbutyric and isobutyric acid, the mutant is also incapable of making the natural avermectins, while supplementation with either one of these compounds restores production of the corresponding four natural avermectins. These facts indicate that in S. avermitilis the branched-chain 2-oxo acid dehydrogenase enzyme functions not only to catabolize the cellular branched-chain amino acids in order to meet energy and growth requirements but also to provide the small branched-chain organic acid precursor molecules necessary for avermectin biosynthesis. Supplementation of the mutant strain with R(-)-2-methylbutyric acid yields novel isomeric avermectins unseen in the (unsupplemented) wild-type strain. It was also concluded that acetate and propionate production by branched-chain 2-oxo acid degradation is not absolutely essential for avermectin production.
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  • CHRISTOPHER J. DUTTON, STEPHEN P. GIBSON, ALEXANDER C. GOUDIE, KELVIN ...
    1991 Volume 44 Issue 3 Pages 357-365
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Avermectins with a wide range of novel C-25 substituents have been prepared by feeding carboxylic acids or their biosynthetic precursors to a Streptomyces avermitilis mutant strain ATCC 53568. This organism lacks the ability to form isobutyric and S-2-methylbutyric acids from their 2-oxo acid precursors and thus is unable to produce natural avermectins unless supplied with these acids. The novel avermectins produced by mutational biosynthesis possess broad-spectrum antiparasitic activity.
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  • HENRY JOSHUA, MICHAEL S. SCHWARTZ, KENNETH E. WILSON
    1991 Volume 44 Issue 3 Pages 366-370
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The microbial transformation of simvastatin (MK-733) by Nocardia autotrophica subspecies amethystina yielded iso-simvastatin-6-one as a minor component. This transformation product is a dienone and is one of the more potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase found to date.
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  • TADASHI FURUMOTO, TADASHI YOSHIOKA, KANAE KAMATA, YUKIHIKO KAMEDA, KAT ...
    1991 Volume 44 Issue 3 Pages 371-373
    Published: March 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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