The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 55 , Issue 4
Showing 1-15 articles out of 15 articles from the selected issue
  • I. Screening, Taxonomy, Fermentation and Biological Activities
    NOBUYASU MATSUURA, NORIMASA TAMEHIRO, TSUTOMU ANDOH, AKIRA KAWASHIMA, ...
    2002 Volume 55 Issue 4 Pages 355-362
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    During the course of our screening for modulators of signal transduction of mammalian cells, we discovered two novel indolocarbazole antibiotics, indocarbazostatin and indocabazostatin B, from a culture broth of a Streptomyces sp. as inhibitors of NGF-induced neuronal differentiation in rat pheochromocytoma PC12 cells. Indocarbazostatin and indocarbazostatin B inhibited NGF-induced neurite outgrowth from PC12 cells at 6nM and 24nM, respectively, whereas K-252a inhibited at 200nM under our assay conditions.
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  • II. Isolation, Physicochemical Properties and Structural Elucidation
    NORIMASA TAMEHIRO, NOBUYASU MATSUURA, YUFEI FENG, NORIYUKI NAKAJIMA, M ...
    2002 Volume 55 Issue 4 Pages 363-370
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Two novel indolocarbazol-type bioactive molecules, indocarbazostatin (1) and indocarbazostatin B (2), were isolated as inhibitors of NGF-induced neuronal differentiation in rat pheochromocytoma PC12 cells from a culture broth of a Streptomyces sp. The structures of these compounds were determined by HR-FAB-MS, UV, 1H and 13C NMR, 1H-1H COSY, PFG HMBC, PFG HMQC and DIF NOE experiments. The relative and absolute configurations were deduced from MM2, MOPAC and CONFLEX calculations, and CD analyses. The imide/amide sector rule was proposed from the analyses of CD data of 1 and other indolocarbazole antibiotics. It was concluded that the minor compound 2 has a negative atropisomeric chirality in the aglycone.
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  • YASUHIRO IGARASHI, AKIRA SEKINE, HIDESUKE FUKAZAWA, YOSHIMASA UEHARA, ...
    2002 Volume 55 Issue 4 Pages 371-376
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    A novel inhibitor for anchorage-independent growth of tumor cells was isolated from the culture broth of a fungal strain. The producing strain TP-F0213 was identified as Penicillium aurantiogriseum Dierckx based on the taxonomic study. The compound designated anicequol was obtained by solvent extraction, HP-20 and silica gel chromatographies and recrystallization. The planar structure was elucidated by NMR analysis to be 16-acetoxy-3, 7, 11-trihydroxyergost-22-en-6-one. The absolute configuration was determined by the X-ray analysis of 3, 7-bis-p-bromobenzoyl derivative. The carbon skeleton of anicequol has the same absolute configuration as ergostane and the configurations of substituents are 3β, 5α, 7β, 11β, 16β and 24S. Anicequol inhibited the anchorage-independent growth of human colon cancer DLD-1 cells with the IC50 of 1.2μM whereas the IC50 against anchorage-dependent growth was 40μM.
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  • PAOLO DAVOLI, GÜNTHER ENGEL, ANDREAS WERLE, OLOV STERNER, TIMM AN ...
    2002 Volume 55 Issue 4 Pages 377-382
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Two novel antifungal agents belonging to the sordarin family have been isolated from fermentations of Sordaria araneosa by bioassay-guided purification and their structures elucidated by NMR techniques. Neosordarin (1) is closely related to the recently discovered hypoxysordarin (2), with only small differences on the aliphatic side chain acylating the hydroxyl in the 3'-position of the sordarose moiety. Hydroxysordarin (3) closely resembles sordarin (4), the only slight difference being the replacement of sordarose with altrose as the sugar unit.
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  • I. Taxonomy, Fermentation, Isolation and Biological Activities
    GLORIA GONZÁLEZ HOLGADO, JULIÁN CASTRO RODRÍGUEZ, ...
    2002 Volume 55 Issue 4 Pages 383-390
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The newly isolated strain Streptomyces sp. RSP9 produces two thiopeptides; one of them is methylsulfomycin I, which shows potent antibiotic activity against several Gram-positive bacteria such as Micrococcus luteus and Staphylococcus aureus. The other is a new thiopeptide named radamycin. In the present work, this compound was purified and tested against several microorganisms and no antibiotic activity was detected in the assays. However, it does have a very strong capacity as an inducer of the tipA promoter, and indeed is the first reported molecule with tipA promoter induction capacity without detectable antibiotic activity. Induction of the tipA promoter also occurs with methylsulfomycin I.
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  • II. Physico-chemical Properties and Structure Determination
    JULIÁN CASTRO RODRÍGUEZ, GLORIA GONZÁLEZ HOLGADO, ...
    2002 Volume 55 Issue 4 Pages 391-395
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The new cyclic peptide antibiotic, radamycin (1) and the known thiopeptide methylsulfomycin I (2) have been isolated from the fermentation broth of a Streptomyces sp. RSP9. The structure of radamycin was elucidated by NMR, LC-MS and FAB-MS and was established as a thiopeptide with oxazole and thiazole moieties, and several unusual amino acids.
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  • ANSGAR STRATMANN, THOMAS SCHUPP, CHRISTIANE TOUPET, WOLFGANG SCHILLING ...
    2002 Volume 55 Issue 4 Pages 396-406
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Proansamycin B, the formerly postulated intermediate of rifamycin B biosynthesis, was isolated from cultures of the Amycolatopsis mediterranei mutant F1/24. The structure was determined using UV, IR, NMR and MS techniques. Biotransformation studies demonstrate that proansamycin B is an intermediate of a shunt pathway, a 8-deoxy variant, of rifamycin B biosynthesis leading to 8-deoxy-rifamycin B as the final product.
    In addition, 34a-deoxy-rifamycin W, the direct precursor of rifamycin W, could be isolated representing the earliest macrocyclic intermediate obtained so far in the biosynthetic route to rifamycin B. Furthermore, the new rifamycin W-28-desmethyl-28-carboxy and rifamycin W-hemiacetal, intermediates in, the transformation sequence of rifamycin W to rifamycin S, were isolated. Application of proton NMR measurements (double resonance and ROESY experiments) on the latter compound indicated that the stereochemistry at the chiral center C-28 is R.
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  • BARBARA WATERS, GEETA SAXENA, YANGSHENG WANGGUI, DAVID KAU, STEPHEN WR ...
    2002 Volume 55 Issue 4 Pages 407-416
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    We have identified a strain of Streptomyces in which aerial hyphae formation appears to be especially sensitive to inhibition by protein kinase inhibitors. Using this assay, a number of bacterial cultures have been screened and novel inhibitors of eukaryotic protein kinases have been identified. Since M. tuberculosis possesses multiple eukaryotic-like protein kinase genes, we tested the active kinase inhibitors for the inhibition of mycobacterial growth and obtained several potent compounds. This identifies a new biochemical class of antimycobacterial agents.
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  • MARIE TOGASHI, HIROMI MASUDA, TERUO KAWADA, MASAO TANAKA, KANAME SAIDA ...
    2002 Volume 55 Issue 4 Pages 417-422
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The prenyl-phenol antibiotics ascochlorin-related compounds, are known to reduce serum cholesterol and triglyceride, suppress hypertension, and ameliorate types-I and II diabetes. However, little is known about the molecular mechanism for these physiological effects. Here we report that the ascochlorin derivative, 4-O-carboxymethyl ascochlorin (AS-6) acts as a potent activator of the nuclear hormone receptor, PPARγ, although it does not activate the related receptors, PPARα, PPARδ or RARα. AS-6 interacts directly with the PPARγ molecule in vitro, and induces differentiation of the mouse preadipocyte cell line 3T3-L1. Our results suggest that AS-6 is a partial agonist for PPARγ with a novel chemical structure.
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  • REBECCA C. GREENWOOD, DANIEL R. GENTRY
    2002 Volume 55 Issue 4 Pages 423-426
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    The compound designated SB-219383 is a potent and selective inhibitor of bacterial tyrosyl tRNA synthetases. It exhibits an IC50 of <1nM against Staphylococcus aureus tyrosyl tRNA synthetase and weak in vitro activity against Staphylococci and Streptococci. Here we present data consistent with SB-219383 eliciting an amino acid starvation in both S. aureus and Streptococcus pneumoniae, supporting the conclusion that the antibacterial activity of SB-219383 is due to tyrosyl tRNA synthetase inhibition.
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  • LAWRENCE C. CREEMER, JOHN E. TOTH, HERBERT A. KIRST
    2002 Volume 55 Issue 4 Pages 427-436
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
    Several series of 14-membered ketolides derived from erythromycin exhibit useful antimicrobial activity against macrolide-resistant bacteria. To determine if 16-membered ketolides may possess analogous activity, 3-keto derivatives of 5-O-mycaminosyl-23-O-acetyltylonolide and desmycosin were synthesized by protection of susceptible functional groups, oxidation of the 3-hydroxyl group under modified Moffatt-Pfitzner conditions, and subsequent deprotection. The resulting 3-keto products unexpectedly adopted the 2, 3-trans enol rather than the 3-keto tautomer. The trans configuration of the 2, 3-double bond in the macrolide chain is most likely the result of hydrogen bond stabilization between the enol hydroxyl and lactone carbonyl, which places these two groups in a cis relationship. This preference for the enol tautomer in 16-membered macrolides is not seen with 14-membered ketolides. The in vitro antimicrobial activity of the enol derivatives was greatly reduced compared to their unoxidized parent compounds, but the reduced antimicrobial activity of the enol derivatives paralleled results from corresponding 2, 3-anhydro derivatives of 16-membered macrolides, which also have 2, 3-trans stereochemistry. These results are in contrast to those from 14-membered-ring macrolides in which 3-keto and 2, 3-anhydro derivatives exhibit greater activity than 3-hydroxy compounds.
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  • MASAHIRO TANAKA, TAKU MORIGUCHI, MASAAKI KIZUKA, YASUNORI ONO, SHUN-IC ...
    2002 Volume 55 Issue 4 Pages 437-441
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
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  • HIKARU NAKAMURA, YOSHIKAZU TAKAHASHI, HIROSHI NAGANAWA, KOICHI NAKAE, ...
    2002 Volume 55 Issue 4 Pages 442-444
    Published: April 25, 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
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  • 2002 Volume 55 Issue 4 Pages C3
    Published: 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
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  • 2002 Volume 55 Issue 4 Pages C4
    Published: 2002
    Released: January 27, 2009
    JOURNALS FREE ACCESS
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