著者
KIMBERLY D. MCBRIEN RONALD L. BERRY SUSAN E. LOWE KIM M. NEDDERMANN ISIA BURSUKER STELLA HUANG STEVEN E. KLOHR JOHN E. LEET
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.48, no.12, pp.1446-1452, 1995-12-25 (Released:2006-04-19)
参考文献数
6
被引用文献数
22 31

The new cytotoxic agents rakicidins A and B were isolated from cultured broth of a Micromonospora sp. Spectroscopic and amino acid analysis has shown that rakicidin A is a new cyclic lipopeptide, consisting of 4-amino-penta-2, 4-dienoic acid, 3-hydroxy-2, 4, 16-trimethylheptadecanoic acid, sarcosine, and 3-hydroxyasparagine. Rakicidin B differs by one methylene group in the lipid side chain. These compounds exhibited cytotoxicity against the Ml09 cell line.
著者
TORU KINO HIROSHI HATANAKA SUSUMU MIYATA NORIAKI INAMURA MICHIHISA NISHIYAMA TOSHIMI YAJIMA TOSHIO GOTO MASAKUNI OKUHARA MASANOBU KOHSAKA HATSUO AOKI TAKENORI OCHIAI
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.40, no.9, pp.1256-1265, 1987-09-25 (Released:2006-04-19)
参考文献数
16
被引用文献数
241 601

The immuno-pharmacological profile of a novel immunosuppressive agent, FK-506 produced by a streptomycete, is presented here. We proceeded to test the effect of the agent on various in vitro immune systems. It showed that mixed lymphocyte reaction, cytotoxic T cell generation, the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 and gamma-interferon and the expression of the IL-2 receptor were suppressed by this agent. The IC50 values of FK-506 and ciclosporin (CS) in all tests were approximately 0.1nM and 10nM, respectively. Therefore, the novel agent, FK-506 suppressed in vitro immune systems at about hundred times lower concentration than CS.
著者
CLAUDE VÉZINA ALICIA KUDELSKI S. N. SEHGAL
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.28, no.10, pp.721-726, 1975 (Released:2006-04-12)
参考文献数
6
被引用文献数
244 717

A streptomycete was isolated from an Easter Island soil sample and found to inhibit Candida albicans, Microsporum gypseum and Trichophyton granulosum. The antibioticproducing microorganism was characterized and identified as Streptomyces hygroscopicus. The antifungal principle was extracted with organic solvent from the mycelium, isolated in crystalline form and named rapamycin. Rapamycin is mainly active against Candida albicans; minimum inhibitory concentration against ten strains ranged from 0.02 to 0.2 μg/ml. Its apparent activity against Microsporum gypseum and Trichophyton granulosum is lower because of its instability in culture media on prolonged incubation required by these fungi. No activity was observed against gram-positive and gram-negative bacteria. Acute toxicity in mice is low.
著者
TOSHIO OTANI YOSHINORI MINAMI TERUYOSHI MARUNAKA Rui ZHANG MEI-YU XIE
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.41, no.11, pp.1580-1585, 1988-11-25 (Released:2006-04-19)
参考文献数
15
被引用文献数
57 55

A new macromolecular antibiotic C-1027 was obtained from the broth filtrate of Streptomyces ghbisporus C-1027 by precipitation with ammonium sulfate, DEAE-cellulose column chromatography and gel filtration chromatography on a Sephadex G-75 column. This antibiotic, prepared as a white powder, is an acidic polypeptide having an isoelectric point of pH 3.5-3.7 and a molecular weight of 15, 000 as determined by SDS-polyacrylamide gel electrophoresis and gel filtration chromatography. The acid hydrolysate of the purified antibiotic C-1027 contained no methionine or tryptophan. From the physico-chemical data, it may be considered to possess a very labile non-protein chromophore.
著者
JILAN HU YU-CHUAN XUE MEI-YU XIE RUI ZHANG TOSHIO OTANI YOSHINORI MINAMI YUJI YAMADA TERUYOSHI MARUNAKA
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.41, no.11, pp.1575-1579, 1988-11-25 (Released:2006-04-19)
参考文献数
14
被引用文献数
77 77

Strain C-1027, an actinomycete isolated from a soil sample collected in China, was found to produce the new antibiotic, C-1027. From taxonomical studies on its morphological, cultural and physiological characteristics, this antibiotic-producing strain was identified as Streptomyces ghbisporus C-1027. Antibiotic C-1027 has antimicrobial activity against most Gram-positive bacteria but not against Mycobacterium sp. or Gram-negative bacteria. This antibiotic shows remarkable activity in spermatogonial assay and potent cytotoxicity against KB carcinoma cells in vitro, and exhibits inhibition on transplantable tumors in mice.
著者
KEISUKE ISHIDA TAKAYUKI TERUYA SIRO SIMIZU HIROYUKI OSADA
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.57, no.2, pp.136-142, 2004-02-25 (Released:2009-01-27)
参考文献数
32
被引用文献数
5 6

In this paper we describe the establishment of an efficient visual method for screening heparanase inhibitors, and we present the results of screening 10, 000 microbial culture broths. Heparanase-overexpressing stable clones of the human hepatocellular carcinoma HepG2 cells were established and used as an enzyme source. Digestion of heparan sulfate (HS) was detected using novel HS-containing tablets or SDS-polyacrylamide gel electrophoresis. This method was able to find suramin, a known heparanase inhibitor, from a library of typical enzyme inhibitors. By screening 10, 000 culture broths of microorganisms (actinomycetes, fungi, and bacteria) an actinomycete strain, RK99-A234, was found to have heparanase inhibitory activity. RK-682 was identified in the fermentation broth as a heparanase inhibitor, IC50=17μM.
著者
TOM S. CHEN BYRON H. ARISON LINDA S. WICKER EDWARD S. INAMINE RICHARD L. MONAGHAN
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.45, no.1, pp.118-123, 1992-01-25 (Released:2006-04-19)
参考文献数
7
被引用文献数
15 12

The immimosuppressants FK506 and FR 900520 were desmethylated by Actinoplanes sp. ATCC 53771 to yield various O-desmethylated products. The products were isolated and purified by solvent extraction and HPLC chromatography, and identified by NMR and MS spectroscopy.
著者
DECENZO MAUREEN KURANDA MIKE COHEN SETH BABIAK JOHN JIANG ZHI-DONG SUN DONGYU HICKEY MARK SANCHETI PRAVEEN BRADFORD PATRICIA A. YOUNGMAN PHIL PROJAN STEVE ROTHSTEIN DAVID M.
出版者
公益財団法人 日本感染症医薬品協会
雑誌
The Journal of Antibiotics
巻号頁・発行日
vol.55, no.3, pp.288-295, 2002
被引用文献数
13

A screening system is described that can detect and confirm inhibitors of the late steps of cell wall biosynthesis. The primary high through-put screen monitors induction of &beta;-lactamase following exposure to samples, in an <i>Escherichia coli envA</i>- strain that carries the &beta;-lactamase gene from <i>Citrobacter freundii</i> on a plasmid. Positive samples were detected from compound libraries, from natural products libraries, and from fractions of natural products crude preparations. These samples were then subjected to <i>in vitro</i> assays that could detect the incorporation of soluble cell wall precursor into Lipid I, Lipid II, and polymerized cell wall, using a TLC system that was very accurate and unambiguous in detecting known cell wall inhibitors. One partially purified sample containing a novel antibacterial agent derived from natural products was found to inhibit the formation of Lipid I (50% inhibition at &le;62.5ng/ml), whereas another partially purified sample also derived from natural products inhibited transglycosylation into cell wall polymer (50% inhibition at &le;10&mu;g/ml). This screening system proved to be especially useful because it was sufficiently sensitive and robust to detect inhibitors among samples of crude preparations or varying states of purity.
著者
ITO-KAGAWA MIKIKO KOYAMA YASUO KONDO SHIGEJI
出版者
公益財団法人 日本感染症医薬品協会
雑誌
The Journal of Antibiotics
巻号頁・発行日
vol.37, no.5, pp.487-493, 1984

Formation of the basic antibiotic, K-582 was stimulated by supplying <i>Metarrhizium anisopliae</i> U-47 with several amino acids present in its structure. The addition of L-arginine to the basal medium resulted in the almost exclusive formation of K-582 B, while L-lysine increased K-582 A formation. Some carbon sources were observed to have effects similar to those obtained with the above mentioned amino acids. Furthermore, when L-arginine was added in excess to the basal medium, free &gamma;-hydroxyarginine, which is a major constituent of the antibiotic, accumulated extra- and intra-cellularly. Free &gamma;-hydroxyarginine isolated from the culture broth of this microorganism was the <i>threo</i>-L-isomer. K-582 formation was repressed by glycerol, which exerted catabolite repression of &gamma;-hydroxyarginine synthesis.
著者
YUSUKE TOKORO TOSHIYUKI ISOE KAZUTOSHI SHINDO
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.52, no.3, pp.263-268, 1999-03-25 (Released:2008-09-19)
参考文献数
5
被引用文献数
7

A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp. QM16. The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis. Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo.
著者
DAVID G. MARTIN CAROLYN BILES SHIRLEY A. GERPHEIDE LADISLAV J. HANKA WILLIAM C. KRUEGER J. PATRICK MCGOVREN STEPHEN A. MIZSAK GARY L. NEIL JULIANNA C. STEWART JERONIMO VISSER
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.34, no.9, pp.1119-1125, 1981 (Released:2006-04-12)
参考文献数
8
被引用文献数
80

( Received for publication June 15, 1981)CC-1065 (NSC 298223) is a potent new antitumor antibiotic with a unique structure produced by Streptomyces zelensis. Improved production, isolation, and assay methods are described along with physico-chemical properties and antitumor activity.
著者
L. J. HANKA A. DIETZ S. A. GERPHEIDE S. L. KUENTZEL D. G. MARTIN
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.31, no.12, pp.1211-1217, 1978 (Released:2006-04-12)
参考文献数
23
被引用文献数
141

A new antitumor antibiotic is produced in fermentation liquors of Streptomyces zelensis sp.n. The antibiotic is biologically active at extremely low concentrations. At 40 pg/ml, it inhibited 90% of the growth of L1210 cells in culture in tube dilution assays. The minimal inhibitory concentrations against Gram-positive bacteria is between 1-10 ng/ml, while these values for Gram-negative bacteria and fungi are mostly under 1 μg/ml. A microbiological assay with Bacillus subtilis can detect concentrations of 1-2 ng/ml.
著者
TOSHIAKI HAYASHI TAKAO NOTO YOSHIHARU NAWATA HIROSHI OKAZAKI MIKIO SAWADA KUNIO ANDO
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.35, no.7, pp.771-777, 1982 (Released:2006-04-12)
参考文献数
17
被引用文献数
16

A new antibiotic, cyanocycline A, was isolated from the fermentation broth of Streptomyces flavogriseus strain No. 49, a soil isolate. The molecular formula of cyanocycline A was determined to be C22H26N4O5. The antibiotic has a cyano group and a N-heterocyclic quinone moiety in its structure. Cyanocycline A was found to have broad spectrum antimicrobial and antitumor activity.
著者
MASAO MIYAUCHI ROKURO ENDO MASAFUMI HISAOKA HIROSHI YASUDA ISAO KAWAMOTO
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.50, no.5, pp.429-439, 1997-05-25 (Released:2006-11-25)
参考文献数
23
被引用文献数
16

We have studied an ester prodrug of a carbapenem to develop a potent orally active β-lactam antibiotic. A variety of 1β-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1R, 5S, 6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(R)-5-oxopyrrolidin-3-ylthio]-1-carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.
著者
IWAO YAMAZAKI YOSHIHIRO SHIRAKAWA TAKESHI FUGONO
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.34, no.11, pp.1476-1485, 1981 (Released:2006-04-12)
参考文献数
18
被引用文献数
2 2

The renal excretory mechanism of cefmenoxime in rabbits was compared with that of 6 other cephalosporins (cefotaxime, deacetylcefotaxime, cefotiam, cefazolin, cephaloridine, and cefsulodin). The clearance ratios (Cf-Drug/CInulin=CRf) of cefmenoxime (337) and cefazolin (73) were considerably higher than those of the 5 other cephalosporins (0.9-20). When p-aminohippurate (PAH) was administered concurrently with each of the cephalosporins, the CRf values of the cephalosporins except for cefsulodin were significantly decreased. These findings indicate that cefmenoxime and the 5 other cephalosporins except cefsulodin are actively incorporated in the proximal tubular cells and secreted into the tubular lumen. In the case of cefotiam and cefsulodin, glomerular filtration tended to exceed urinary excretion with the highest dose of PAH (40 mg/kg/minute), suggesting the possibility of tubular reabsorption of these drugs. On the other hand, glomerular filtration of cefmenoxime and the 4 other cephalosporins did not exceed urinary excretion. The drug concentration ratio of the cortex to medulla indicated that the tubular cell level of cefmenoxime was lower than, higher than, and similar to those of cephaloridine, cefotaxime, and the remaining cephalosporins, respectively. These results demonstrate that the renal excretory mechanism of cefmenoxime is similar to that of cefazolin but not to that of the remaining cephalosporins.