The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 43 , Issue 12
Showing 1-21 articles out of 21 articles from the selected issue
  • MITSUNOBU HARA, TSUYOSHI MOKUDAI, EIJI KOBAYASHI, KATSUSHIGE GOMI, HIR ...
    1990 Volume 43 Issue 12 Pages 1513-1518
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    As a result of screening for antitumor agents from actinomycetes, the kepurimycins were isolated from Streptomyces sp. DO-115. The antibiotics were produced in a fermentation medium supplemented with high porous polymer resin which adsorbs antibiotics and results in an increase of titer. The active complex was isolated from the polymer resin by a solvent extraction procedure and was separated by column chromatography, into two minor and one major component, named A1, A2 and A3. The kepurimycins were active against bacteria, particularly Gram-positive organisms, and were cytotoxic to HeLa S3 human cerivical cancer cells and T24 human bladder carcinoma cells in vitro. Among the individual components of the kapurimycins, kapurimycin A3 exhibited the strongest antibacterial and cytotoxic activities. It showed a potent antitumor activity against murine leukemia P388 in vivo.
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  • MAYUMI YOSHIDA, MITSUNOBU HARA, YUTAKA SAITOH, HIROSHI SANO
    1990 Volume 43 Issue 12 Pages 1519-1523
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The kapurimycins A1, A2 and A3 were revealed to be new antitumor antibiotics with molecular formula of C27H26O9, C26H24O9 and C27H24O9, respectively. The structures of the kapurimycins were determined by NMR spectroscopic analysis. The kapurimycins are new class of polycyclic microbial metabolites having the tetrahydroanthra-γ-pyrone skeleton and the β, γ-unsaturated δ-keto carboxylic acid structure. The individual components of the kapurimycins differ from one another in the side chain at the pyrone ring of the molecule.
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  • HIROSHI ITAZAKI, KAZUO NAGASHIMA, KENJI SUGITA, HIROSHI YOSHIDA, YOSHI ...
    1990 Volume 43 Issue 12 Pages 1524-1532
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    New cyclotetrapeptides, trapoxins A and B were isolated from the culture broth of Helicoma ambiens RF-1023. These compounds exhibit detransformation activities against v-sis oncogenetransformed NIH3T3 cells (sis/NIH3T3) as antitumor agents. The structures were found to be new cyclotetrapeptides, cyclo[(S)-phenylalanyl-(S)-phenylalanyl-(R)-pipecolinyl-(2S, 9S)-2-amino-8-oxo-9, 10-epoxydecanoyl-] for trapoxin A and cyclo[(S)-phenylalanyl-(S)-phenylalanyl-(R)-prolyl-2-amino-8-oxo-9, 10-epoxydecanoyl-] for trapoxin B, by X-ray analysis, mass spectrometric, NMR and chemical studies.
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  • HISAO KONDO, SHIGERU NAKAJIMA, NAOKO YAMAMOTO, AKIRA OKURA, FUMIO SATO ...
    1990 Volume 43 Issue 12 Pages 1533-1542
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Streptomyces graminofaciens BA14348, isolated from a soil sample, was found to produce new specific inhibitors of estrogen binding to its receptor. Five related substances, BE-14348A-E, were isolated, and their structures were determined by analyses of spectral properties. Of these substances, A was identical with the known flavanone, naringenin. On the other hand, B, C, D and E were all new compounds; the structure of B was determined to be 2(S):3(S)-3-methyl-4', 5, 7-trihydroxyflavanone, C was a racemic mixture of 2(S):3(R) and 2(R):3(S)-3-methyl-4', 5, 7-trihydroxyflavanone; D and E were 8-chloro derivatives of B and C, respectively.
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  • N. RAMA KRISHNA, DONALD M. MILLER, TED T. SAKAI
    1990 Volume 43 Issue 12 Pages 1543-1552
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The assignments for the resonances in the 1H and 13C NMR spectra of mithramycin in aqueous solution have been determined by a combination of 2D NMR methods. Specific NOESY contacts observed between different moieties indicate that the drug assumes a compact conformation in aqueous solution. Fluorescence measurements are consistent with a compact structure for mithramycin in water and confirm the preference of mithramycin for binding to dG-containing nucleic acids. These studies provide a basis for the further physico-chemical characterization of mithramycin-DNA complexes.
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  • HIDETOSHI KUMAGAI, HIROYUKI NISHIDA, NOBUTAKA IMAMURA, HIROSHI TOMODA, ...
    1990 Volume 43 Issue 12 Pages 1553-1558
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structures of atpenins A4, A5 and B, new antifungal antibiotics produced by Penicillium sp., have been deduced to be I, II and III, respectively, on the basis of spectroscopic and 1H and 13C NMR spectral data. The molecular structure of atpenin A4 with absolute configurations was finally confirmed to be 2'S, 4'S', 5'S-5, 6-dimethoxy-4-hydroxy-5'-chloro-2', 4'-dimethyl-r-oxoheptyl-2-hydroxypyridine (I') by the single crystal X-ray crystallographic analysis. The absolute configurations of atpenins A5 and B were also expected to be 2'S, 4'S, 5'R-II (II') and 2'S, 4'R-III (III'), respectively.
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  • JAVIER MARTÍN-VILLACORTA, ANGEL REGLERO, MIGUEL A. FERRERO, JOS ...
    1990 Volume 43 Issue 12 Pages 1559-1563
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Three different hexenoyl-CoA derivatives (trans-2-hexenoyl-CoA, trans-3-hexenoyl-CoA and trans-trans-2, 4-hexadienoyl-CoA), two octenoyl-CoA (trans-2-octenoyl-CoA, trans-3-octenoyl-CoA) and 2-octynoyl-CoA were tested as substrates of the enzyme acyl-CoA: 6-Aminopenicillanic acid acyltransferase (AT) from Penicillium chrysogenum. Only trans-3-hexenoyl-CoA and trans-3-octenoyl-CoA were recognized by AT and efficiently converted into penicillin F and octenoylpenicillin, respectively. The Km values for these substrates were 0.6 and 0.5 mM, suggesting that the affinity of AT for these molecules is similar to that reported for phenyl acetyl-CoA, octanoyl-CoA and hexanoyl-CoA (0.5, 0.6, and 1 mM, respectively). The absence of enzymatic activity shown by AT with the other acyl-CoA derivatives tested is due to the different position of the double or triple bond(s) in their aliphatic chains. The influence of the free rotation round the bond C-2-C-3 and possibility of planar conformation in such molecules and the importance in the formation of the enzyme-substrate complex is discussed.
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  • HAJIME KAMACHI, TAKAAKI OKITA, SATSUKI OKUYAMA, HIDEAKI HOSHI, TAKAYUK ...
    1990 Volume 43 Issue 12 Pages 1564-1572
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    1-Acetoxyethyl 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-[(Z)-1-propenyl]-3-cephem-4-carboxylate (BMY-28271) is an ester-type prodrug of cephalosporin for oral use. Methods suitable for large scale preparation were investigated. The yield was improved by esterification of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-trityloxyiminoacetamido]cephem-4-carboxylic acid (11) followed by removal of the trityl group and, in addition, column chromatographic purification at each step was eliminated by optimization of the reaction conditions.
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  • NAOHIKO YAMAMOTO, YOSHINARI YAMADA, TOHRU DAIKOKU, YUKIHIRO NISHIYAMA, ...
    1990 Volume 43 Issue 12 Pages 1573-1578
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The antiviral activity of a new guanosine analog, 9-(2-deoxy-2-hydroxymethyl-βD-erythro-oxetanosyl)guanine (OXT-G), against guinea pig cytomegalovirus (GPCMV) was evaluated both in vitro and in vivo. In the plaque reduction assay, the median effective concentration (EC50) of OXT-G, ganciclovir (DHPG) and acyclovir (ACV) against GPCMV was 0.03, 6.4 and 52 μg/ml, respectively. The selectivity index, based on the ratio of the median inhibitory concentration for cell growth of guinea pig embryo fibroblasts to the median effective concentration for GPCMV plaque formation, was about 100-fold higer than that of DHPG. In an in vivo study, Hartley guinea pigs infected with GPCMV were treated with OXT-G or DHPG (20 mg/kg/day) for 2 weeks, and it was found that virus titers in the salivary gland were 70-fold lower in OXT-G-treated guinea pigs than in DHPG-treated animals. The results indicate that OXT-G was more potent and selective against GPCMV infection than DHPG.
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  • SONOKO ATSUMI, HIRONOBU IINUMA, CHISATO NOSAKA, KAZUO UMEZAWA
    1990 Volume 43 Issue 12 Pages 1579-1585
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Cyclophellitol ((1S, 2R, 3S, 4R, 5R, 6R)-5-hydroxymethyl-7-oxabicyclo[4, l, 0]heptane-2, 3, 4-triol) was tested against 9 glycosidases and found to be a specific inhibitor of almond β-glucosidase. Cyclophellitol inhibited almond β-glucosidase activity by 50% at 0.8 μg/ml and was a competitive inhibitor of almond β-glucosidase as revealed by Lineweaver-Burk plot. Cyclophellitol was inactive against yeast α-glucosidase, β-galactosidase, β-glucuronidase, α-L-fucosidase, end-β-N-acetyl glucosaminidase, α-mannosidase, and cellulase. It was weakly active toward fungal β-xylosidase. Cyclophellitol-treated almond β-glucosidase was equally suppressed after dialysis; thus cyclophellitol is likely to bind to almond β-glucosidase irreversibly. The inhibitor was found by fluorimetric assay to be active against β-glucosidase but inactive toward α-glucosidase in Molt-4 microsomal fraction. It also inhibited Molt-4 β-glucocerebrosidase completely at 2 μg/ml when the enzyme was assayed with a synthetic labeled substrate, and the inhibitory activity was more than one hundred times higher than that of nojirimycin, castanospermine, or of deoxynojirimycin. Mice administered 1 mg of cyclophellitol daily for 5 days began to exhibit severe abnormalities of nervous system similar to those found in GAUCHER'S mouse.
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  • HIROSHI NISHIOKA, TSUTOMU SAWA, MASA HAMADA, NAOMI SHIMURA, MASAYA IMO ...
    1990 Volume 43 Issue 12 Pages 1586-1589
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    We have screened toyocamycin as an inhibitor of phosphatidylinositol kinase. It inhibited the enzyme of A431 cell membrane with an IC50 of 3.3 μg/ml. Adenosine and formycin A also inhibited the enzyme, but other 6 related nucleosides did not. Although orobol and 2, 3-dihydroxybenzaldehyde that inhibit phosphatidylinositol kinase inhibited in situ phosphatidylinositol turnover, toyocamycin did not.
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  • KYUICHI NEMOTO, TAKAKO MAE, YUMI SUGAWARA, MICHIKO HAYASHI, FUMINORI A ...
    1990 Volume 43 Issue 12 Pages 1590-1596
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The present study was designed to evaluate the therapeutic activity of a novel immunosuppressive agent, deoxyspergualin (DSG, NKT-01) in male MRL/MpJ-lpr/lpr (MRL/lpr) mice suffering advanced systemic lupus erythematosus (SLE)-like lesions. Treatment with DSG in the early phase of the disease at doses of 1.5 and 3mg/kg strongly suppressed the development of SLE-like lesions. When DSG was administered from week 21 through 29 to MRL/lpr mice in advanced phases of the disease, a daily iv dose of 3 mg/kg (5 days/week) markedly reduced the symptoms, whereas a dose of 1.5 mg/kg did not. Moreover, DSG treatemt at a dose of 3mg/kg, started at the time when the blood urea nitrogen levels were over 50 mg/deciliter, significantly prevented deterioration of the hyperuremia. Taking these findings into consideration, DSG was found to be a promising agent for curing such established autoimmune disease.
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  • TEIICHI NAKAMURA, DAISUKE KOMAGATA, SHIGEO MURAKAWA, KAORU SAKAI, AKIR ...
    1990 Volume 43 Issue 12 Pages 1597-1600
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    3α-Hydroxy-3, 5-dihydromonacolin L acid (acid form), a new compound related to monacolin K (mevinolin), was isolated from the culture broth of a strain of Monascus ruber. The structure of the compound was determined by a combination of physical techniques. 4a, 5-Dihydromonacolin L was converted to 3α-hydroxy-3, 5-dihydromonacolin L by a cell-free extract of M. Ruber in the presence of molecular oxygen. The results demonstrate that the former is the direct precursor in the biosynthesis of the latter.
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  • KOJI TOMITA, NAHOMI ODA, MASARU OHBAYASHI, HIDEO KAMEI, TAKEO MIYAKI, ...
    1990 Volume 43 Issue 12 Pages 1601-1605
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    A novel screening method for melanin biosynthesis inhibitors using Streptomyces bikiniensis NRRL B-1049 as the indicator organism has been developed.
    Several known compounds, including tyrosinase inhibitors, were found to inhibit melanin production of S. bikiniensis on agar plates. This screening method was applied to fermentation broths of actinomycetes and several cultures with melanin biosynthesis inhibitory activity were found.
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  • SHINSUKE IMAI, AKIRA SHIMAZU, KEIKO FURIHATA, KAZUO FURIHATA, YOICHI H ...
    1990 Volume 43 Issue 12 Pages 1606-1607
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • RIE TANAKA, HIROMITSU IWATA, MASAJI ISHIGURO
    1990 Volume 43 Issue 12 Pages 1608-1610
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • EIJIRO UMEMURA, TSUTOMU TSUCHIYA, KOICHI TANAKA, SUMIO UMEZAWA
    1990 Volume 43 Issue 12 Pages 1611-1614
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • OSAMU NAKAYAMA, MASASHI YAGI, SUMIO KIYOTO, MASAKUNI OKUHARA, MASANOBU ...
    1990 Volume 43 Issue 12 Pages 1615-1616
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • TERUTAKA HASHIZUME, MINORU SANADA, SUSUMU NAKAGAWA, NOBUO TANAKA
    1990 Volume 43 Issue 12 Pages 1617-1620
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • KEISUKE KIMURA, DAISUKE KOMAGATA, SHIGEO MURAKAWA, AKIRA ENDO
    1990 Volume 43 Issue 12 Pages 1621-1622
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • MIYUKI KANEDA, TOSHIHARU KITAHARA, KAZUO YAMASAKI, SHOSHIRO NAKAMURA
    1990 Volume 43 Issue 12 Pages 1623-1626
    Published: December 25, 1990
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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