The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 43 , Issue 4
Showing 1-17 articles out of 17 articles from the selected issue
  • TERUAKI OZASA, KENICHI SUZUKI, TOSHIMITSU YAMADA, KIYOSHI SUZAKI, CHIE ...
    1990 Volume 43 Issue 4 Pages 331-335
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Placetins, platelet aggregation inhibitors were obtained from the culture broth of Streptomyces sp. Q-1043. These were designated placetins A, Al, B and Bl, respectively. Placetins A and B showed strong cytotoxicities against P388, L1210 and HeLa cells.
    Download PDF (228K)
  • TOHRU YASUZAWA, YUTAKA SAITOH, HIROSHI SANO
    1990 Volume 43 Issue 4 Pages 336-343
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structures of KS-501 and KS-502, new inhibitors of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase, were determined to be 2-(β-D-galactofuranosyloxy)-6-heptyl4-hydroxybenzoic acid 3-heptyl-5-hydroxyphenyl ester and 2-(β-D-galactofuranosyloxy)-6-heptyl-4-hydroxybenzoic acid 4-carboxy-3-heptyl-5-hydroxyphenyl ester, respectively, on the basis of chemical and physico-chemical evidences.
    Download PDF (458K)
  • ITSUO UCHIDA, SEIJI HASHIMOTO, TOSHIRO IWAMOTO, SHIGEHIRO TAKASE, MASA ...
    1990 Volume 43 Issue 4 Pages 344-351
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structures of compounds 3 (and 4) and 5 (and 6) derived from the natural products WS1358A1 (1) (and Bl (2)) have been determined by their spectroscopic evidence. By taking advantage of these transformations, an improved synthesis of Al (1, racemate) has been achieved.
    Download PDF (446K)
  • MIKIO KITAHARA, KATSUHIRO SHINJYO, MASAFUMI FUKAE, KAZUNORI HOSOE, TAD ...
    1990 Volume 43 Issue 4 Pages 352-356
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    We prepared new 7-hydroxyguanine derivatives, 7-hydroxyguanosine 5'-monophosphate and N2-tetrahydropyranyl-7-hydroxyguanine, and compared biological activities of 7-hydroxyguanine derivatives including nucleosides acquired previously. 7-Hydroxyguanine and its nucleotide inhibited the focus formation of Rous sarcoma virus. Antitumor activities of these derivatives against mouse leukemia L1210 were not so different from one another. Anti-proliferative activities of the derivatives on various human cell lines were significantly different from one another.
    Download PDF (312K)
  • TSUNEO OKONOGI, SEIJI SHIBAHARA, YASUSHI MURAI, TAKASHI YOSHIDA, SHIGE ...
    1990 Volume 43 Issue 4 Pages 357-371
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    New 2-methyl-1-oxacephem compounds having 2-(2-aminothiazol-4-yl)-2-(alkoxyimino)acetamido substituents at C-7 and various C-3 side chains were synthesized starting from (3R, 4S)-phenyloxazolinoazetidinone (8). Introduction of the 2β-methyl group into the 1-oxacephem nucleus increased the stability to β-laetamases. OCP-9-176 (7b) having the (l-methylpyridinium-4-yl)thiomethyl group at C-3 showed potent antibacterial activity and a broad spectrum.
    Download PDF (989K)
  • KENJI KON, HIDEO SUGI, KIYOSHI TAMAI, YOSHIMICHI UEDA, NOBUTOSHI YAMAD ...
    1990 Volume 43 Issue 4 Pages 372-382
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    In order to overcome the rapid biliary excretion of chartreusin, which diminished its activity when administered iv, a series of 3', 4'-O-substituted derivatives of chartreusin were synthesized. Exo-type of 3', 4'-O-benzylidene-chartreusin was found active both by ip and iv administration. Therefore, this compound was selected for further modification on its 6-phenol to obtain broader spectra and better pharmacokinetic parameters than the original compound. Several 6-O-acyl-3', 4'-O-exo-benzylidene-chartreusins had high antitumor activity against some murine tumors both by iv and po administration.
    Download PDF (643K)
  • MOTOMICHI KONO, MASAJI KASAI, KUNIKATSU SHIRAHATA, MAKOTO MORIMOTO
    1990 Volume 43 Issue 4 Pages 383-390
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Mitomycin G (2) was derived from porfiromycin (10b) in 3 steps via the methanesulfonate (14b) in an overall yield of 39%. On the basis of the established method for the introduction of an exomethylene group in mitomycins with a 9a-methoxy group, the preparation of biologically more important la-demethylmitomycin G (5) from mitomycin C (1) was accomplished by the use of a protective acetyl group on the aziridine in an overall yield of 57%. la-Demethylmitomycin K (6) was obtained from 5 in a yield of 42%. In a preliminary evaluation of their antitumor activity, compound 5 showed superior activity against sarcoma 180 (sc-ip) to its la-methyl congener, i.e., mitomycin G (2).
    Download PDF (472K)
  • SHIZUKO KAKINUMA, HARUO IKEDA, SATOSHI OMURA, DAVID A. HOPWOOD
    1990 Volume 43 Issue 4 Pages 391-396
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The mutants of Streptomyces tanashiensis strain Kala, which were specifically blocked in the synthesis of the benzoisochromanequinone antibiotic kalafungin, were isolated and classified into seven phenotypic classes on the basis of the antibiotic activity and cosynthetic properties. The polarity of cosynthetic reactions and the production of kalafungin by a converter strain showed that the seven mutant classes could be arranged in the most probable linear sequence of biosynthetic blocks. Since kalafungin, which closely resembles the undimerized form of actinorhodin, was accumulated in one of the biosynthetically blocked mutants of the actinorhodin-producing Streptomyces coelicolor A3(2), the cosynthesis between kalafungin-nonproducing mutants of S. tanashiensis and actinorhodin-nonproducing mutants of S. coelicolor was performed. The results of these experiments showed that the early steps in kalafungin biosynthesis in S. tanashiensis and actinorhodin biosynthesis in S. coelicolor were similar, but the entire biosynthetic pathway of kalafungin in these two streptomycetes was not identical.
    Download PDF (335K)
  • HIDETOSHI KUMAGAI, HIROSHI TOMODA, SATOSHI OMURA
    1990 Volume 43 Issue 4 Pages 397-402
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A new screening method for specific inhibitors of mevalonate biosynthesis was established using Vero cells, an animal cell line. The cultures selected were those which inhibited the growth of Vero cells in the EAGLE'S minimum essential medium supplemented with 2% calf serum (2% CS-MEM) but lacked inhibitory activity against the growth of cells in 2% CS-MEM supplemented with 1 mM mevalonate. By this screening method, inhibitors of the two enzymes involved in mevalonate biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and HMG-CoA reductase, were selected from about 11, 000 soil isolates. The β-lactone 1233A, a fungal metabolite, was found to be the first naturally occurring compound which inhibits HMG-CoA synthase specifically and strongly. Monacolins K and J, inhibitors of HMG-CoA reductase, were also detected and identified.
    Download PDF (621K)
  • YUKO SAKURAI, YUKIE YOSHIDA, KEIKO SAITOH, MAYUMI NEMOTO, AKIHITO YAMA ...
    1990 Volume 43 Issue 4 Pages 403-410
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Aztreonam was investigated as to its characteristics as a substrate, inhibitor and inducer for the well-defined β-lactamases of Gram-negative bacteria, and its antibacterial efficacy as to bacterial cells producing eight types of β-lactamases was also evaluated. Aztreonam was hydrolyzed at measurable rates by class A β-lactamases, a TEM-2 type penicillinase and the Proteus vulgaris cephalosporinase with a broad substrate range. However, the affinity of aztreonam for the class A enzymes was low, this property being well reflected by its high antibacterial activity toward producers of class A β-lactamases. Aztreonam was extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acted as a competitive and progressive inhibitor for the β-lactamase. While the MICs of aztreonam in the cases of the constitutive producers of class C β-lactamases were evidently affected by enzyme production. An experiment involving aztreonam as a inhibitor in combination with a hydrolyzable β-lactam gave ambiguous results, however, a strong synergistic effect was found in combination with mecillinam. Using Pseudomonas aeruginosa, aztreonam was confirmed to be a poor inducer of β-lactamases.
    Download PDF (458K)
  • MAKI YAMAGUCHI, HIROSHI YAMAKI, TAKAKO SHINODA, YOSHITAKA TAGO, HIDEO ...
    1990 Volume 43 Issue 4 Pages 411-416
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    An antifungal amino acid antibiotic, (S)2-amino-4-oxo-5-hydroxypentanoic acid (RI-331) isolated from Streptomyces sp., inhibited the biosynthesis of protein to a greater extent than that of RNA or DNA in growing Saccharomyces cerevisiae cells. Polypeptide biosynthesis in a cell-free system from the yeast was refractory to the antibiotic, suggesting the possibility that the biosynthesis of one or more amino acids might be inhibited. Intracellular amino acid pools, particularly those of methionine, isoleucine and threonine were significantly reduced when yeast cells were incubated in the presence of RI-331. Consistent with this, the growth-inhibitory activity of RI-331 was markedly reversed by the addition of these amino acids into the growth medium, and an even greater effect was exerted by homoserine which works as a common metabolic precursor for these amino acids in yeasts. It looks likely therefore that the inhibition of biosyntheses of some or all of these amino acids by RI-331 is primarily responsible for overall inhibition of protein biosynthesis in yeasts, ultimately leading to cytostasis. This possible mechanism of RI-331 action appears to explain favorably the selective toxicity of the antibiotic against yeasts, since mammalians lack enzymatic systems for synthesizing methionine, isoleucine and threonine which are required as essential amino acids for growth.
    Download PDF (385K)
  • YOSHIKAZU SUGIMOTO, TOSHIO OTANI, SHINJI OIE, KONSTANTY WIERZBA, YUJI ...
    1990 Volume 43 Issue 4 Pages 417-421
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    C-1027 is a new antitumor protein antibiotic containing a non-protein chromophore. The active moiety and the mechanism of action of this antibiotic were studied. C-1027 and its chromophore inhibited the growth of KB carcinoma and LI 210 leukemia cells, even at extremely low concentrations. C-1027 inhibited DNA synthesis of L1210 cells and cleaved cellular DNA in a drug concentrationdependent manner. C-1027 and chromophore caused directly DNA single strand breaks in the purified DNA without any supplement of reducing agents. These results suggest that C-1027 chromophore may inhibit cell growth by causing DNA breakage with subsequent inhibition of DNA synthesis.
    Download PDF (366K)
  • THOMAS GOOTZ, DENNIS GIRARD, WILLIAM SCHELKLEY, THOMAS TENSFELDT, GEOR ...
    1990 Volume 43 Issue 4 Pages 422-432
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The pharmacokinetics of penem CP-65, 207 diastereomeric mixture were studied following parenteral administration in mice, rats, beagle dogs and cynomolgus monkeys. As is characteristic for most penems, the serum elimination T1/2 of CP-65, 207 in rodents was only 13 minutes for mice and 18 minutes for rats. A linear relationship was observed between dose and Cmax following subcutaneous injection of drug in mice. The T1/2 in the beagle dog and monkey following intravenous injection was approximately 23 minutes. CP-65, 207 demonstrated binding to human serum proteins of only 10%. In vitro studies using purified porcine renal dehydropeptidase-I (RDHP) indicated that the pure S-isomer of CP-65, 207 was 7-fold more stable to inactivation than imipenem. Urinary recovery of CP-65, 207 in the dog was 42% compared to 1% for imipenem without RDHP inhibitor. Unlike results obtained with imipenem, coadministration of probenecid with CP-65, 207 in the dog doubled the elimination T1/2 and AUC of the penem demonstrating its relative stability in vivo in the absence of a RDHP inhibitor. The pivaloyloxymethyl esters of each pure isomer of CP-65, 207 showed significantly different degrees of oral absorption in rats.
    Download PDF (688K)
  • CATHY S. TAFT, CLAUDE P. SELITRENNIKOFF
    1990 Volume 43 Issue 4 Pages 433-437
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Download PDF (346K)
  • MING-S. T. KUO, DAVID A. YUREK, ALICE L. LABORDE, SCOTT E. TRUESDELL, ...
    1990 Volume 43 Issue 4 Pages 438-440
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Download PDF (166K)
  • YOSHIKAZU TAKAHASHI, HIKARU NAKAMURA, RIE OGATA, NAOKO MATSUDA, MASA H ...
    1990 Volume 43 Issue 4 Pages 441-443
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Download PDF (177K)
  • KAZUO SHIN-YA, SHINSUKE IMAI, KAZUO FURIHATA, YOICHI HAYAKAWA, YOKO KA ...
    1990 Volume 43 Issue 4 Pages 444-447
    Published: April 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Download PDF (232K)
feedback
Top