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ALEXANDRA GEHRT, GERHARD ERKEL, TIMM ANKE, OLOV STERNER
1998 Volume 51 Issue 5 Pages
455-463
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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In a screening for new inhibitors of NF-κB and AP-1 mediated signal transduction pathways in COS-7 cells using secreted alkaline phosphatase (SEAP) as a reporter gene three novel compounds, cycloepoxydon (
1), 1-hydroxy-2-hydroxymethyl-3-pent-1-enylbenzene (
2) and 1-hydroxy-2-hydroxymethyl-3-pent-1, 3-dienylbenzene (
3) were isolated from fermentations of the deuteromycete strain
45—93. Cycloepoxydon inhibits the TPA-induced NF-κB and AP-1 mediated SEAP expression with an IC
50 of 1∼2 μg/ml (4.2∼8.4 μM) and 3∼5 μg/ml (12.6∼21 μM) respectively. 1-Hydroxy-2-hydroxymethyl-3-pent-1-enylbenzene (
2) inhibits the TPA-induced NF-κB and AP-1 mediated SEAP expression with an IC
50 of 7 μg/ml (36.4 μM) and 5 μg/ml (26 μM).
3 showed only a weak inhibition of the AP-1 and no influence on NF-κB dependent reporter gene expression. In COS-7 and HeLa S3 cells electrophoretic mobility shift assays showed that cycloepoxydon strongly reduced the TPA and TNF-α mediated binding of NF-κB to a high affinity consensus sequence which was due to the inhibition of phosphorylation of the inhibitory protein IκB.
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Taxonomy, Fermentation, Isolation, Physico-chemical Properties, Structure Elucidation and Biological Activity
VINOD R. HEGDE, MAHESH G. PATEL, ANN C. HORAN, ARTHUR H. KING, FRANK G ...
1998 Volume 51 Issue 5 Pages
464-470
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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A novel secondary metabolite SCH 42282 (
1), with antifungal activity was isolated from the fermentation broth of a soil actinomycete identified as a
Microtetraspora sp. The active compound was separated from the fermentation broth by butanol extraction and purified on a silica gel column and by multi-coil counter current chromatography. The compound was identified as a novel macrolactam trisaccharide related to SCH 38518 (
4). The structure was established by hydrolysis of the parent compound and spectroscopic studies of the acetate derivative. The compound is active against
Candida spp. (Geometric Mean MIC's, 18 μg/ml) but less active than SCH 42729 (
3), the disaccharide (Geometric Mean MIC's, ≥10.7 μg/ml) and SCH 38518 (
4), the monosaccharide (Geometric Mean MIC's, 3.8 μg/ml).
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Cell Wall Transglycosylation Inhibitors in Enterococcus
NAGRAJ MANI, PRAVEEN SANCHET, ZHI-DONG JIANG, COLLEEN MCNANEY, MAUREEN ...
1998 Volume 51 Issue 5 Pages
471-479
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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We devised two screening systems to detect cell wall transglycosylation inhibitors. One screen utilizes a mutant of
Enterococcus faecalis strain A256 that is dependent on vancomycin or moenomycin for growth. In the absence of transglycosylation inhibitors the strain fails to grow, while in the presence of inhibitors, cells are rescued. A second screening organism
E.
faecalis strain MDD212 utilizes a translational fusion of the
lacZ gene to the
vanH promoter in a derivative of
E.
faecalis that contains a vancomycin resistance determinant. Induction of β-galactosidase occurs when cells are exposed to inhibitors of transglycosylation. Our natural products drug source of fungal fermentations was tested with these screens. Several cultures that produced the same family of compounds, called the thielavins, were detected. Thielavin B inhibited the formation of peptidoglycan in an
in vitro assay, suggesting that these screening systems can detect compounds that interfere with cell wall transglycosylation.
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MAKOTO CHINO, KIYOHIRO NISHIKAWA, AYUMI YAMADA, MICHIYO OHSONO, TSUTOM ...
1998 Volume 51 Issue 5 Pages
480-486
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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Heliquinomycin, a novel microbial product, was found to inhibit a human DNA helicase enzyme isolated from HeLa S3 cells at concentrations of 5 to 10 μg/ml. In contrast, adriamycin, etoposide and cisplatin did not inhibit this enzyme at the concentrations tested. Furthermore, the replication and repair of SV40 chromosome were not affected at heliquinomycin concentration of 50 μg/ml. The topoisomerase II and I enzymes were inhibited at 30 μg/ml and 100 μg/ml of heliquinomycin, respectively. Heliquinomycin inhibited the growth of HeLa S3, KB, LS180, K562 and HL60 human tumor cell lines at IC
50 values of 0.96 to 2.8 μg/ml. In addition, the growth of adriamycin and cisplatin resistant P388 cell lines were inhibited at similar concentrations. Heliquinomycin inhibited both DNA and RNA synthesis in cell culture but did not inhibit protein synthesis. HeLa S3 cells were arrested at the G
2/M phase by heliquinomycin. These studies suggest that heliquinomycin is a selective inhibitor of a cellular DNA helicase and in turn, inhibits growth of tumor cell lines.
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GRACE K. WONG, STEPHEN GRIFFITH, IKUO KOJIMA, ARNOLD L. DEMAIN
1998 Volume 51 Issue 5 Pages
487-491
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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The antifungal agent rapamycin is highly effective in inhibiting growth of yeast and mold strains. This study demonstrates that in liquid medium, rapamycin is more active than its derivatives (prolylrapamycin, 32-desmethylrapamycin, 32-desmethoxyrapamycin) against
Candida albicans,
Saccharomyces cerevisiae, and
Fusarium oxysporum. All the rapamycins were more active than amphotericin B. Although four other molds were not inhibited in liquid medium, they were very sensitive to rapamycin and its derivatives when tested on agar. The latter assay showed that rapamycin is the most active and 32-desmethylrapamycin is more active than prolylrapamycin and 32-desmethoxyrapamycin. The conclusion of this study is that rapamycin is the most active antifungal agent of the compounds examined. The unexpected finding of high activity of rapamycin and its derivatives against filamentous fungi when assayed by the agar diffusion assay suggests that rapamycin or a derivative may hold promise for chemotherapy against pathogenic molds as well as yeasts.
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YOSHITOMO IKAI, HISAO OKA, JUNKO HAYAKAWA, NORIHISA KAWAMURA, TSUYOSHI ...
1998 Volume 51 Issue 5 Pages
492-498
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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Structural characterization of the colistin (CL) components were carried out using Frit-fast atom bombardment liquid chromatography/mass spectrometry (Frit-FAB LC/MS), tandem mass spectrometry (MS/MS) and the amino acid analysis proposed by MARFEY, and the total structures of 4 minor components including the absolute configuration of the constituent amino acids were proposed. The structures of the minor components were the same as those of the main component colistin A or B except that L-leucine is replaced by L-valine or L-isoleucine.
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OLAF KINZEL, ROBERT TAPPE, IGOR GERUS, HERBERT BUDZIKIEWICZ
1998 Volume 51 Issue 5 Pages
499-507
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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Two pyoverdin-ampicillin conjugates were synthesized and their structures were confirmed by mass spectrometry and NMR spectroscopy. In contrast to ampicillin, the conjugates exhibited high antibacterial activity against
Pseudomonas aeruginosa ATCC 15692 and ATCC 27853, effective only against the strain which is using the parent pyoverdin for iron uptake. This suggests that the conjugates enter the bacterial cell
via the ferripyoverdin uptake pathway. Growth stimulation studies with conjugates hydrolysed at the β-lactam ring of the ampicillin moiety supported this view.
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SHUJI JINNO, KAZUHIKO HATA, NOBUYOSHI SHIMIDZU, TAKAAKI OKITA
1998 Volume 51 Issue 5 Pages
508-511
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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GERARD HELYNCK, CATHERINE DUBERTRET, DENISE FRECHET, JEAN LEBOUL
1998 Volume 51 Issue 5 Pages
512-514
Published: May 25, 1998
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KHISAL A. ALVI, ALLEN CASEY, BIPIN G. NAIR
1998 Volume 51 Issue 5 Pages
515-517
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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BIBORKA ENGEL, GERHARD ERKEL, TIMM ANKE, OLOV STERNER
1998 Volume 51 Issue 5 Pages
518-521
Published: May 25, 1998
Released on J-STAGE: January 27, 2009
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E. K. S. VIJAYAKUMAR, KIRITY ROY, SUGATA CHATTERJEE, TRIPTIKUMAR MUKHO ...
1998 Volume 51 Issue 5 Pages
522-524
Published: May 25, 1998
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ANDREI Y. PAVLOV, MARIA N. PREOBRAZHENSKAYA, ADRIANO MALABARBA, ROMEO ...
1998 Volume 51 Issue 5 Pages
525-527
Published: May 25, 1998
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ALBERT HÄRTL, A. STELZNER, MICHAEL RITZAU, STEFAN HEINZE, UDO GR& ...
1998 Volume 51 Issue 5 Pages
528-530
Published: May 25, 1998
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1998 Volume 51 Issue 5 Pages
C1a
Published: 1998
Released on J-STAGE: January 27, 2009
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1998 Volume 51 Issue 5 Pages
C1b
Published: 1998
Released on J-STAGE: January 27, 2009
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1998 Volume 51 Issue 5 Pages
C1c
Published: 1998
Released on J-STAGE: January 27, 2009
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