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AUGUST J. KEMPF, KENNETH E. WILSON, OTTO D. HENSENS, RICHARD L. MONAGH ...
1986 Volume 39 Issue 10 Pages
1361-1367
Published: 1986
Released on J-STAGE: April 19, 2006
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L-681, 217 is a new broad spectrum antibiotic isolated from fermentation broth. The compound is a structurally unique member of the efrotomycin family of growth permittant antibiotics.
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I. TAXONOMY, FERMENTATION, ISOLATION AND BIOLOGICAL PROPERTIES
YOSHINORI INAOKA, HIDETSUNE TAMAOKI, SHUJI TAKAHASHI, RYUZO ENOKITA, T ...
1986 Volume 39 Issue 10 Pages
1368-1377
Published: 1986
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A soil isolate of actinomycete, strain SANK 60684, was found to produce new enkephalinase B inhibitors, propioxatins A and B. The presence of both LL- and meso-2, 6-diaminopimelic acid, glycine and galactose in the cell wall assigned this strain to genus
Kitasatosporia. From the morphological, cultural and physiological characteristics, this strain was determined to be
Kitasatosporia setae. The
Ki values of propioxatins A and B were 1.3×10
-8 M and 1.1×10
-7 M, respectively, for enkephalinase B. All other proteases examined except aminopeptidases, which were slightly inhibited, were not inhibited by these two compounds.
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II. STRUCTURAL ELUCIDATION
YOSHINORI INAOKA, SHUJI TAKAHASHI, TAKESHI KINOSHITA
1986 Volume 39 Issue 10 Pages
1378-1381
Published: 1986
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The structures of propioxatins A (C
17H
29N
3O
6) and B (C
18H
31N
3O
6), new enkephalinase B inhibitors produced by
Kitasatosporia setae SANK 60684, were determined. Both propioxatins consist of
N-acyl-L-prolyl-L-valine.
N-Acyl moieties of propioxatins A and B were α-propyl and α-isobutyl succinic acid β-hydroxamic acid, respectively.
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III. TOTAL SYNTHESIS OF PROPIOXATIN A
YOSHINORI INAOKA, SHUJI TAKAHASHI, SADAO SATO
1986 Volume 39 Issue 10 Pages
1382-1385
Published: 1986
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Propioxatin A, a potent enkephalinase B inhibitor produced by
Kitasatosporia setae SANK 60684, was synthesized. The synthetic route involved a regio-selective synthesis of
O-benzyl-α-propylsuccinic acid monohydroxamic acid
via the acid chloride of α-propylsuccinic acid. The stereoisomer of the
N-acyl moiety of natural propioxatin A was analyzed by X-ray crystallography in the form of the di-
O-benzyl ester and was determined as
S. Devalyl propioxatin A synthesized by the same method showed a higher
Ki value for enkephalinase B than propioxatin A.
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I. DISCOVERY, PRODUCTION, AND BIOLOGICAL EVALUATION
M. C. SHEARER, A. J. GIOVENELLA, S. F. GRAPPEL, R. D. HEDDE, R. J. MEH ...
1986 Volume 39 Issue 10 Pages
1386-1394
Published: 1986
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A new subspecies of
Kibdelosporangium aridum subsp.
largum (SK&F AAD-609), was isolated and shown to produce novel glycopeptides related to aridicins, but containing a homologous series of glycolipids based on
N-acylglucosamine. These compounds showed improvements over the aridicins in
in vitro activity and were effective in mouse protection studies against a range of Gram-positive bacteria, including methicillin resistant staphylococci. Pharmacokinetic studies indicated that they have high serum concentrations and long-acting potential. The kibdelin complex modified rumen metabolism in a manner favorable for growth promotion.
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II. ISOLATION, PURIFICATION AND STRUCTURE
G. FOLENA-WASSERMAN, B. L. POEHLAND, E. W-K. YEUNG, D. STAIGER, L. B. ...
1986 Volume 39 Issue 10 Pages
1395-1406
Published: 1986
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A new glycopeptide antibiotic complex was isolated from the fermentation culture of
Kibdelosporangium aridum subsp. largum (SK&F AAD-609) by affinity chromatography on a D-alanyl-D-alanine agarose column. The major components of the complex were resolved by preparative reversed-phase HPLC. Mild acid hydrolysis showed that the new antibiotics have the same mannosyl aglycon (
2) as the aridicins. FAB mass spectrometry, isoelectric
focusing, potentiometric titration and carbohydrate and fatty acid analyses were used to determine the structures of the five major components of the complex. These studies showed that the kibdelins differ from the aridicins only in the oxidation level at the C-6 position of the amino sugar. Kibdelin A (
5), B (
6), C
1 (
7), C
2 (
8) and D (
9) are a series of
N-acylglucosamine analogs containing saturated straight and branched chain C
10-C
12 fatty acids whereas, in kibdelin D the fatty acid component is (
Z)-4-decenoic acid.
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I. PRODUCTION, ISOLATION, AND PHYSICO-CHEMICAL AND BIOLOGICAL PROPERTIES
SATOSHI OMURA, NOBUTAKA IMAMURA, RUIKO OIWA, HIROSHI KUGA, RIMIKO IWAT ...
1986 Volume 39 Issue 10 Pages
1407-1412
Published: 1986
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A soil isolate named as
Micromonospora echinospora subsp.
armeniaca subsp. nov. KMR-593 was found to produce at least five related antibiotics, clostomicins, active against Gram-positive bacteria including anaerobes. From the physico-chemical properties, one of these components was identified with lipiarmycin and others were found to be new antibiotics. Each component includes two chlorine atoms and the molecular weights of A and B
2, C, and D are 1, 058, 1, 042 and 1, 056, respectively. The structural differences were characterized by NMR analyses.
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II. TAXONOMIC STUDY OF THE PRODUCING MICROORGANISM
YOKO TAKAHASHI, YUZURU IWAI, SATOSHI OMURA
1986 Volume 39 Issue 10 Pages
1413-1418
Published: 1986
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Taxonomic properties of actinomycete strain KMR-593, a soil isolate, which produces new anti-anaerobe antibiotics, clostomicins, were investigated. The strain was identified as a new subspecies of the genus
Micromonospora and designated
Micromonospora echinospora subsp.
armeniaca subsp. nov.
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II. SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF 6β-(2-ARYL-2-SULFOACETAMIDO)-6α-METHOXY PENICILLANIC ACIDS
GEORGE BURTON, DESMOND J. BEST, RONALD A. DIXON, ROBERT F. KENYON, AND ...
1986 Volume 39 Issue 10 Pages
1419-1429
Published: 1986
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The synthesis and antibacterial activity of 6α-methoxysulbenicillin analogues (
2) are described. Structure-activity studies of these derivatives bearing hydrophilic substituents in the phenyl ring led to the identification of disodium 6β-[D-2-(3, 4-dihydroxyphenyl)-2-sulfoacetamido]-6α-methoxypenicillanate (
2m) as a compound with potent activity against
Pseudomonas aeruginosa including β-lactamase producing strains. Additional substitution of
2m gave derivatives
2p, 2q, 2r, with a further improvement in activity against Gram-negative bacteria.
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VII. PREPARATION AND NMR CHARACTERISTICS OF THE AGLYCONE OF TEICOPLANIN
ADRIANO MALABARBA, PIETRO FERRARI, GIAN GUALBERTO GALLO, JURGEN KETTEN ...
1986 Volume 39 Issue 10 Pages
1430-1442
Published: 1986
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Several hydrolytic reactions that transform teicoplanin or its pseudo-aglycones into the aglycone with good yields are described. The most interesting approach is hydrolytic removal of the sugars in benzyl alcohol with the formation of the aglycone benzyl ester which is then submitted to hydrogenolysis. A detailed description of the 1H and 13C NMR spectra of the teicoplanin aglycone hydrochloride is presented. All the signals were attributed to the hydrogen
and carbon atoms using homo and heteronuclear COSY. The relevant interactions through space between the hydrogen atoms were obtained by NOE. The structural aspects are discussed in terms of the well-known mechanism of action of the glycopeptide antibiotics.
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MITUO OGURA, TERUO TANAKA, KEIKO FURIHATA, AKIRA SHIMAZU, NOBORU OTAKE
1986 Volume 39 Issue 10 Pages
1443-1449
Published: 1986
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Protoplast regeneration carried out in a carriomycin producing organism,
Streptomyces hygroscopicus 358 AV2, lose carriomycin productivity without loss of carriomycin-resistance and the ability of formation of aerial mycelium. Ethidium bromide treatment on the 358 AV2 strain generated a bald mutant that produced carriomycin and a new antibiotic curromycin. In some other media, however, the parent strain produced curromycin, indicating that the ethidium bromide treatment altered the regulation of antibiotic production. Ethidium bromide treatment on a protoplast-regenerated strain derived from the parent strain resulted in derivatives capable of producing carriomycin and curromycin. These strains were unstable and tended to lose the recovered antibiotic productivity easily.
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TAKAO KASAI, TAKESHI NISHINO, YUZO KAZUNO, TERUO TANINO
1986 Volume 39 Issue 10 Pages
1450-1460
Published: 1986
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The efficacy of BRL28500, a formulation of ticarcillin (TIPC, 15 parts) and clavulanic acid (CVA, 1 part), against TIPC-resistant strains of
Staphylococcus aureus, Escherichia coli and
Klebsiella pneumoniae was studied both
in vitro and
in vivo. The MICs of BRL28500 against these β-lactamase producing strains were lower than those of TIPC or CVA alone against such strains. When BRL28500 was added during the logarithmic growth phase of bacteria at a concentration equivalent to the MIC, it demonstrated marked lytic activity. Cells treated with BRL28500 underwent morphological change, becoming filament-like, similar to those treated with TIPC alone. With CVA alone at concentrations above the MIC the cells assumed a stable round form. In bacterial cultures of the β-lactamase-producing strains, TIPC was protected from hydrolysis by the presence of CVA. The
in vivo activity of BRL28500 against experimental infections in mice caused by β-lactamase-producing strains of bacteria was superior to that of TIPC alone. TIPC and CVA were found to be well distributed in peritoneal fluid following subcutaneous administration of BRL28500 into mice with peritoneal infections. The residual TIPC concentrations achieved were higher than when TIPC alone was administered. These results suggest that BRL28500 will be effective in the treatment of human infections due to TIPC-resistant bacteria.
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KIYOHIRO NISHIKAWA, CHIEKO SHIBASAKI, KATSUTOSHI TAKAHASHI, TERUYA NAK ...
1986 Volume 39 Issue 10 Pages
1461-1466
Published: 1986
Released on J-STAGE: April 19, 2006
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Spergualin (SGL), a novel antitumor antibiotic, exhibited strong antitumor activity against transplantable leukemias in mice: L1210, L1210(IMC), P388, P815, C1498, EL-4 and RL ♂ 1. It also exhibited antitumor activity against M5076 fibrosarcoma, AH66 and AH66F rat hepatomas, but not against Meth-A fibrosarcoma, B16 melanoma, Lewis lung carcinoma (LL) and C26 colon adenocarcinoma. The antitumor activity of SGL was administration-schedule dependent. The strongest activity against L1210 was obtained by ip continuous infusion for 7 days or daily ip administration for 9 days. Single ip injection of SGL
at 100 mg/kg to mice caused convulsion and death within 15 minutes after injection. Such acute toxicity was not observed by continuous infusion. SGL showed its strongest activity at subtoxic dose against sensitive tumors except for L1210(IMC). Mice implanted ip with L1210(IMC) were cured by treatment with SGL at 3.13 mg/kg/day for 9 days, but died from the tumor at 50 mg/kg/day ×9. The cured mice rejected a second inoculation of up to 10
6 tumor cells. The tumor cells isolated from mice after treatment with the high dose showed resistance to SGL
in vivo. Mice implanted sc with L1210(IMC) were also cured by 9 daily ip administrations of SGL at 12.5 mg/kg/day, but solid tumor was observed at the implantation site until 3 days after the final injection of SGL in some cured mice. These results suggest that the therapeutic effect of SGL has a relatively high specificity for leukemias and that the immunological effect is involved in the antitumor activity.
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STEPHEN W. MAMBER, WANDA G. OKASINSKI, CHERYL D. PINTER, JOSEFINO B. T ...
1986 Volume 39 Issue 10 Pages
1467-1472
Published: 1986
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The novel fermentation products fostriecin and analogs PD 113, 270 and PD 113, 271 are structurally related polyene lactone phosphates that have antitumor activity
in vitro and
in vivo. They have no antibacterial effects, but they were inhibitory to yeasts (agar diffusion method) with MICs of 3-300 μg/ml. Fostriecin or its analogs were active vs. 29 of 46 yeast species (11 genera). Ten of 12 cultures of
Candida sp. were not sensitive to any of the analogs, while 11 of 14 cultures of
Saccharomyces sp. were inhibited by one or more of the agents. Sensitivity patterns were of three types: Twelve cultures were sensitive only to PD 113, 270; fostriecin and PD 113, 271 (but not PD 113, 270) were active vs. 7 cultures; and 9 cultures were sensitive to all three compounds. Dephosphorylation of the compounds resulted in the loss of antimycotic effects. Activity vs. the yeasts was related to studies of uptake and activity against cancer cells.
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KATSUTOSHI TAKAHASHI, TOMOHISA TAKITA, HAMAO UMEZAWA
1986 Volume 39 Issue 10 Pages
1473-1478
Published: 1986
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Effects of
o-phenanthroline, 2, 2'-dipyridyl and neocuproine, which form stable complexes preferentially with Fe(II), Fe(II) and specifically with Cu(I), respectively, on the inhibitory activity of bleomycin against DNA synthesis of rat ascites hepatoma AH66 cells were examined. The inhibitory activity of metal-free bleomycin was suppressed in the presence of
o-phenanthroline or 2, 2'-dipyridyl, but not by neocuproine, though these chelating agents also showed the inhibitory activity against the DNA synthesis of the cells by themselves alone. The activity of bleomycin-Cu(II) was also suppressed by
o-phenanthroline, but bleomycin-Fe(II) and bleomycin-Fe(III) exhibited some activities in the presence of
o-phenanthroline. The growth inhibitory activity of bleomycin against HeLa cells was also suppressed by
o-phenanthroline. From these results, bleomycin-iron complexes were suggested to be responsible to the bleomycin action in cells.
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IV. SYNTHESIS AND IN VITRO ANTIVIRAL ACTIVITY OF NEW N -PALMITOYLKANAMYCIN A DERIVATIVES
KEIJI MATSUDA, NOBUYOSHI YASUDA, HIDEO TSUTSUMI, TAKAO TAKAYA
1986 Volume 39 Issue 10 Pages
1479-1482
Published: 1986
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M. J. Jr. ZMIJEWSKI, B. BRIGGS, J. OCCOLOWITZ
1986 Volume 39 Issue 10 Pages
1483-1485
Published: 1986
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KENNETH R. STEWART
1986 Volume 39 Issue 10 Pages
1486-1487
Published: 1986
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JUNPEI ITO, TAKUMI YAMASHITA, KATSUTOSHI TAKAHASHI, HIROO HORINISHI, T ...
1986 Volume 39 Issue 10 Pages
1488-1490
Published: 1986
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YUKIHIKO KAMEDA, NAOKI ASANO, TAKUJI YAMAGUCHI, KATSUHIKO MATSUI, SATO ...
1986 Volume 39 Issue 10 Pages
1491-1494
Published: 1986
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III. ACCUMULATION OF 3a-HYDROXY-6-FLUOROINDOLINE UPON ADDITION OF 6-FLUOROTRYPTOPHAN TO THE CULTURED BROTH OF STREPTOMYCES SP. H-63
AKIRA KAWASHIMA, HARUO SETO, MASAO KATO, ARATA YASUDA, KEIICHI UCHIDA, ...
1986 Volume 39 Issue 10 Pages
1495-1497
Published: 1986
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ANGELA W. GUEST, FRANK P. HARRINGTON, PETER H. MILNER, ROGER J. PONSFO ...
1986 Volume 39 Issue 10 Pages
1498-1501
Published: 1986
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MICHAEL J. DRIVER, JOHN LOWTHER
1986 Volume 39 Issue 10 Pages
1502-1504
Published: 1986
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HIROYOSHI TOHYAMA, YOSHIRO OKAMI, HAMAO UMEZAWA
1986 Volume 39 Issue 10 Pages
1505-1507
Published: 1986
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