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HIROYUKI OSADA
1998 Volume 51 Issue 11 Pages
973-982
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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Bioprobes are low molecular weight compounds which are useful for investigating mammalian cell functions. The use of bioprobes has substantially assisted the investigation of complex biochemical processes of the mammalian cell cycle. In this review, cell cycle inhibitors mainly isolated from the microorganism are described and their possibility as an antitumor agents is considered. Most cancer cells have some abnormality in the control mechanism of cell cycle progression. Cyclin-dependent kinases (Cdk), which are activated by the binding with the cyclin and simultaneously by the phosphorylation/dephosphorylation of itself, play important roles as engines in the cell cycle. Tubulins are considered to be one of the most important proteins of the cell division machinery. Therefore, Cdk inhibitors and tubulin binders are possible anticancer drugs. Since the function of proteins controlling the cell cycle is also regulated by phosphorylation and dephosphorylation, inhibitors of protein kinases and phosphatases are considered as possible an antitumor agents. We expect that some bioprobes will be developed for clinical use.
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TOSHIYUKI SAITO, FUKUMATSU AOKI, HIDEO HIRAI, TAISUKE INAGAKI, YASUE M ...
1998 Volume 51 Issue 11 Pages
983-990
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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A κ opioid receptor binding inhibitor was isolated from the fermentation broth of a basidiomycete,
Hericium ramosum CL24240 and identified as erinacine E (
1). Three analogs of
1 were produced by fermentation in other media and by microbial biotransformation. Of these compounds,
1 was shown to be the most potent binding inhibitor. Preliminary SAR studies of these compounds indicated that all functional groups and side chains were required for the activity. Compound
1 was a highly-selective binding inhibitor for the κ opioid receptor: 0.8 μM (IC
50) for κ, > 200 μM for μ, and > 200 μM for δ opioid receptor. Compound
1 suppressed electrically-stimulated twitch responses of rabbit vas deferens with an ED
50 of 14 μM. The suppression was recovered by adding a selective κ opioid receptor antagonist nor-binaltorphimine, indicating that
1 is a κ opioid receptor agonist.
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I. Taxonomy, Fermentation, Isolation and Biological Activities
KEITAROU SUZUKI, KAZUHIKO NAGAO, YUTAKA MONNAI, AKEMI YAGI, MASARU UYE ...
1998 Volume 51 Issue 11 Pages
991-998
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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A novel inhibitor of topoisomerases designated as topostatin was isolated from the culture filtrate of
Thermomonospora alba strain No. 1520. Topostatin inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase I, and also inhibited the relaxation of supercoiled pBR322 DNA and decatenation of kinetoplast DNA by human placenta topoisomerase II. Topostatin had neither ability to stabilize the cleavable complex nor ability to intercalate into DNA strands. The inhibitor exhibited growth inhibitory activity against the tumor cells (SNB-75 and SNB-78) of central nervous system, but did not exhibit any antimicrobial activity against Gram-positive and Gram-negative bacteria, yeasts and fungi.
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II. Physico-chemical Properties and Structure Elucidation
KEITAROU SUZUKI, SHOJI YAHARA, YUTAKA KIDO, KAZUHIKO NAGAO, YUICHI HAT ...
1998 Volume 51 Issue 11 Pages
999-1003
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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Topostatin is a new topoisomerase inhibitor isolated from the culture filtrate of
Thermomonospora alba strain No. 1520. The inhibitor inhibits topoisomerases I and II, and it has neither ability to stabilize the cleavable complex nor ability to intercalate into DNA strands. The molecular formula of topostatin was determined as C
36H
58N
4O
11S based on the FAB-MS analyses, and the structure was elucidated to be a novel 14-membered ring containing peptide and terpenoid by various NMR spectroscopies.
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KEIICHI MATSUZAKI, HARUMI TAHARA, JUNJI INOKOSHI, HARUO TANAKA, ROKURO ...
1998 Volume 51 Issue 11 Pages
1004-1011
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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Novel brominated and halogen-less azaphilone (oxoisochromane) derivatives, 5-bromoochrephilone and dechloroisochromophilone IV, and known derivatives, dechloroisochromophilone III and isorotiorin, were isolated from the culture broth of a producing organism of isochromophilones I and II (azaphilones inhibiting gp120-CD4 binding),
Penicillium multicolor FO-2338, fermented in a medium containing potassium bromide. Nineteen azaphilone-related compounds isolated from the above strain and from other fungi were tested for the inhibition of gp120-CD4 binding and the structure-activity relationship is discussed. Consequently, 5-bromoochrephilone is the strongest inhibitor (IC
50, 2.5 μM). A halogen atom at C-5, a proton at C-8 and a diene structure in C-3 side chain of 6-oxoisochromane ring are necessary for gp120-CD4 binding.
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Isolation, Characterisation and Biological Properties
TRACY C. KENNEDY, GRAHAM WEBB, RICHARD J. P. CANNELL, OONAGH S. KINSMA ...
1998 Volume 51 Issue 11 Pages
1012-1018
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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The isolation and structure determination of 6 analogues of the fungal protein synthesis inhibitor GR135402, from
Graphium putredinis, is described. The relative potencies of the compounds as protein synthesis inhibitors and as
in vitro antifungal agents provide interesting insights into the structure-activity relationships in this series.
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Novel Inhibitors of Aflatoxin Production by Aspergillus parasiticus
MAKOTO ONO, SHOHEI SAKUDA, HIROYUKI IKEDA, KAZUO FURIHATA, JIRO NAKAYA ...
1998 Volume 51 Issue 11 Pages
1019-1028
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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Two novel inhibitors of aflatoxin production by
Aspergillus parasiticus were isolated from the mycelial extracts of
Streptomyces sp. MRI142 and termed aflastatin A and B. The structures of aflastatin A (
1) and B (
5) were elucidated by NMR and chemical degradation experiments. These compounds have a novel skeleton of a tetramic acid derivative with a highly oxygenated long alkyl chain. The incorporation experiments using
13C-labeled acetates, propionate, glucose and glycolate suggested that most of the C
2 and C
3 units involved in the alkyl chain moiety of aflastatin A were biosynthesized from acetic and propionic acids, but five C
2 units in the alkyl chain originated from glycolic acid.
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I. Fermentation, Isolation and Biological Activity
MICHAEL S. PACEY, JOHN P. DIRLAM, RODERICK W. GELDART, PETER F. LEADLA ...
1998 Volume 51 Issue 11 Pages
1029-1034
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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In a previous report, a plasmid, pIG1, which contained the loading domain from the
Streptomyces avermitilis polyketide synthase (PKS), promoters from
Streptomyces coelicolor and the DEBS1-TE truncated PKS from
Saccharopolyspora erythraea, was integrated into the
S.
erythraea chromosome, effectively replacing the natural erythromycin loading domain with the avermectin loading domain. In this paper, we report the feeding of short-chained fatty acids to this recombinant strain, and its parent, NRRL 2338. Both strains incorporated exogenously supplied fatty acids to produce novel, biologically active, C-13 substituted erythromycins.
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II. Biological Properties
KAZUMI YOKOMIZO, YOSHIAKI MIYAMOTO, KAZUHIKO NAGAO, ETSUKO KUMAGAE, EL ...
1998 Volume 51 Issue 11 Pages
1035-1039
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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Fattiviracin A1, showed potent antiviral activities against herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), influenza A virus and human immunodeficiency virus type 1 (HIV-1). It showed no cytotoxicity against Vero cells. Fattiviracin A1 exhibited no significant antibacterial or antifungal activities. Treatment of HSV-1 with fattiviracin A1 decreased its infectivity to Vero cells. The mechanism of its antiviral activity may be due to inactivation of the viral particles and inhibition of viral entry into host cells.
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ALBERT HÄRTL, AXEL STELZNER, ROLF SCHLEGEL, STEPHAN HEINZE, HEIKE ...
1998 Volume 51 Issue 11 Pages
1040-1046
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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II. Structure Elucidation
TAKAAKI SATO, TOSHIHIKO HANADA, MANABU ARIOKA, TETSU-ICHIRO MORITA, HI ...
1998 Volume 51 Issue 11 Pages
1047-1050
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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SENJI TAKAHASHI, KENICHI UCHIDA, NORIHIRO KAKINUMA, RYUJU HASHIMOTO, T ...
1998 Volume 51 Issue 11 Pages
1051-1054
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
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HEIKE HÜLSMANN, STEPHAN HEINZE, MICHAEL RITZAU, BRIGITTE SCHLEGEL ...
1998 Volume 51 Issue 11 Pages
1055-1058
Published: November 25, 1998
Released on J-STAGE: January 27, 2009
JOURNAL
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