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 29

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
241 589

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
244 679

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
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 5

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
12

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
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.
著者
TREW SALLY J. WRIGLEY STEPHEN K. PAIRET LYDIE SOHAL JESS SHANU-WILSON PATRICK HAYES MARTIN A. MARTIN STEVEN M. MANOHAR RAVI N. CHICARELLI-ROBINSON M. INÊS KAU DAVID A. BYRNE COLIN V WELLINGTON ELIZABETH M. H. MOLONEY JANET M. HOWARD JUDITH HUPE DONALD OLSON ERIC R.
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.53, no.1, pp.1-11, 2000
被引用文献数
25

A series of halogenated pyrrolo [2, 1-b] [1, 3] benzoxazines (<b>1</b>-<b>9</b>) was isolated from fermentations of an actinomycete strain X10/78/978 (NCIMB40808), identified as <i>Streptomyces rimosus</i>, during a microbial extract screening programme to identify inhibitors of bacterial histidine kinase. The structures of these compounds were elucidated by spectroscopic methods including the HMQC, HMBC and INADEQUATE NMR experiments. The structure of <b>1</b> was confirmed by X-ray crystallographic studies. Compounds <b>5</b> and <b>6</b> were produced in fermentations in the presence of NaBr and Nal respectively. The most abundant member of the series, streptopyrrole, <b>1</b>, inhibited the nitrogen regulator II (NRII) histidine kinase from <i>Escherichia coli</i> with an IC<sub>50</sub> of 20μM and exhibited antimicrobial activity against a range of bacteria and fungi.
著者
MASARU YOSHIDA MASAMI EZAKI MICHIZANE HASHIMOTO MICHIO YAMASHITA NOBUHARU SHIGEMATSU MASAKUNI OKUHARA MASANOBU KOHSAKA KOKI HORIKOSHI
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.43, no.7, pp.748-754, 1990-07-25 (Released:2006-04-19)
参考文献数
12
被引用文献数
46 56

Streptoverticillium fervens produced a new antibiotic, FR-900848, which has a high specific activity against filamentous fungi. Purified by solvent extraction and column chromatography, the compound appears as colorless crystals. Its structure is C32H43N3O6, which consists of 5'-amino-5'-deoxy-5, 6-dihydrouridine with an unsaturated fatty acid having unprecedented four serial and one isolated cyclopropane rings.
著者
YASUHIRO IGARASHI KATSUYUKI FUTAMATA TSUYOSHI FUJITA AKIRA SEKINE HISATO SENDA HIDEO NAOKI TAMOTSU FURUMAI
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.56, no.2, pp.107-113, 2003-02-25 (Released:2009-01-27)
参考文献数
9
被引用文献数
38 53

In the screening of novel antifungal compounds, yatakemycin was found in the culture broth of Streptomyces sp. TP-A0356. Yatakemycin was obtained by solvent extraction of the fermentation broth and chromatographic purification using ODS column and preparative HPLC. The structure of yatakemycin was elucidated by NMR and CID-MS/MS experiments as a novel antibiotic belonging to a family of CC-1065 and duocarmycins known to be DNA alkylating agents. Yatakemycin inhibited the growth of pathogenic fungi such as Aspergillus fumigatus and Candida albicans with the MIC values of 0.01-0.03μg/ml, more potent than amphotericin B (MIC: 0.1-0.5μg/ml) or itraconazole (MIC: 0.03-0.2μg/ml). It also showed potent cytotoxicity against cancer cell lines with the IC50 of 0.01-0.3μg/ml.
著者
S. N. SEHGAL H. BAKER Claude VÉZINA
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.727-732, 1975 (Released:2006-04-12)
参考文献数
7
被引用文献数
42 449

Rapamycin is a new antifungal antibiotic produced by Streptomyces hygroscopicus NRRL 5491. It was isolated from the mycelium by solvent extraction, purified by silica gel column chromatography and crystallized as a colorless solid which melts at 183-185°C and has the empirical formula C56H89NO14. From its characteristic ultraviolet absorption spectrum rapamycin can be classified as a triene. It is highly active against various Candida species, especially Candida albicans. Its activity is compared with that of amphotericin B, candicidin and nystatin.
著者
KAYOKO SUZUKAKE-TSUCHIYA MAKOTO HORI NOBUYOSHI SHIMADA MASA HAMADA
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.41, no.5, pp.675-683, 1988-05-25 (Released:2006-04-19)
参考文献数
6
被引用文献数
3 2

Deoxypheganomycin D, a specific inhibitor of mycobacteria, inhibits the growth in vitro of Mycobacterium smegmatis ATCC 607 (M. 607) bacteriostatically at concentrations as high as 7×10-5M. It shows no cross-resistance to paromomycin, capreomycin, viomycin, streptothricin, kanamycin and streptomycin. Deoxypheganomycin D at 2.8×10-7M where the cell growth of M. 607 is only partially inhibited does not significantly inhibit DNA, RNA or protein synthesis but leads to marked decrease (13 % of control) in [14C]glycerol-derived radioactivity in cell-walls. In the presence of 7×10-6M deoxypheganomycin D, the influx of leucine but not thymidine is affected while the reverse is true with efflux. The data suggest that the effect of deoxypheganomycin D on M. 607 may be related to both the cell membrane and specific mycobacterial lipid like components of the cell-wall.
著者
KIYOSHI TSUJI JOHN F. GOETZ
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.31, no.4, pp.302-308, 1978 (Released:2006-04-12)
参考文献数
16
被引用文献数
27 30

Reverse phase high performance liquid chromatography (HPLC) was used as a rapid means of monitoring the erythromycin and the tetracycline fermentation processes. The sample preparation process for tetracycline in the fermentation broth includes simple dilution and filtration through a Millipore filter prior to injection into the HPLC column. Fermentation broth samples showed no interference, and excellent separation for selective determination of tetracycline, 4-epitetracycline, anhydrotetracycline, chlortetracycline, and 4-epianhydrotetracycline was obtained. The relative standard deviation for the HPLC analysis for tetracycline is about one percent and the correlation coefficient between the HPLC and the spectrophotometric assay methods is better than 0.994.The sample preparation procedure for erythromycin determination in fermentation broth requires solvent cleanup and extraction processes. The chromatographic analysis takes approximately 25 minutes, and the HPLC method is capable of separating and quantifying erythromycins A, B, C, and various epimers and degradation compounds. The correlation coefficient between the HPLC and the microbiological assay method is 0.970.
著者
MIKIO SAWADA TOMOYOSHI HOSOKAWA TSUNEO OKUTOMI KUNIO ANDO
出版者
JAPAN ANTIBIOTICS RESEARCH ASSOCIATION
雑誌
The Journal of Antibiotics (ISSN:00218820)
巻号頁・発行日
vol.26, no.11, pp.681-686, 1973-11-25 (Released:2006-04-12)
参考文献数
15
被引用文献数
24 18

Ascofuranone significantly reduced serum lipid levels of rats fed with normal diet 6 hours after a single oral administration of 108 mg/kg. When the antibiotic was orally given for consecutive 10 days to normolipidemic rats, the treatment resulted in marked reduction of serum cholesterol, triglycerides, phospholipids and free fatty acids without affecting organ weight gain, serum total protein, albumin/globulin ratio and serum transaminases. Reduction was also noted with cardiac cholesterol content but liver total sterol and fecal sterol excretion were unchanged. Acute toxicity of ascofuranone is weak to mice and rats and the antibiotic did not induce hepatomegaly which is the main side effect of a positive control agent, ethyl-p-chlorophenoxyisobutyrate.