The Journal of Antibiotics
Online ISSN : 1881-1469
Print ISSN : 0021-8820
ISSN-L : 0021-8820
Volume 44 , Issue 10
Showing 1-20 articles out of 20 articles from the selected issue
  • MEGUMI MIYOSHI-SAITOH, NAOKO MORISAKI, YOSHIYUKI TOKIWA, SHIGEO IWASAK ...
    1991 Volume 44 Issue 10 Pages 1037-1044
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    New antibiotics, dynemicins O (3), P (4) and Q (5), were isolated from the culture broth of Micromonospora chersina M956-1, the dynemicin A (1)-producing strain.
    An ethyl acetate extract of a tank culture was roughly separated by a column of Diaion SP-800 and was further purified by combining a variety of column chromatographies to afford a few mg of compounds 3, 4 and 5. Their structures, analyzed from the spectral data, had a bridging phenylene group, a vic-diol and an oxo group in place of the respective 1, 5-diyn-3-ene bridge, the epoxide ring and the carboxyl group in dynemicin A. Their biological activities were evaluated against bacteria and tumor cells.
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  • MICHIO ICHIMURA, TATSUHIRO OGAWA, SHIGEO KATSUMATA, KEI-ICHI TAKAHASHI ...
    1991 Volume 44 Issue 10 Pages 1045-1053
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Six duocarmycins have been discovered during our search for new antitumor antibiotics and they showed extremely potent cytotoxic activity with IC50 values of 10-12 M-10-9M on HeLa S3 cell. Three different producing strains isolated from soils were taxonomically assigned as Streptomyces. Duocarmycin A was unstable in culture broth, so improved culture conditions were designed to produce a high titer of duocarmycins B1, B2, C1 and C2 which are halogenated seco-compounds of duocarmycin A. Duocarmycin SA, one of the most potent cytotoxic agents yet discovered, was shown to be more stable in culture media than duocarmycin A, despite the structural similarity on their spirocyclopropylhexadienone moiety. In contrast to the duocarmycin A fermentation, no halogenated seco-compounds of duocarmycin SA were detected in culture broth supplemented with Br- or Cl-. All duocarmycins could be produced using one producing strain with improved media and culture conditions.
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  • KATSUHISA KOJIRI, HIROHARU ARAKAWA, FUMIO SATOH, KENJI KAWAMURA, AKIRA ...
    1991 Volume 44 Issue 10 Pages 1054-1060
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    New antitumor substances, designated BE-12406A and BE-12406B, were isolated from the culture broth of a streptomycete, strain BA12406. The active principles were extracted from mycelium by methanol and successively purified by silica gel column chromatography and preparative TLC. BE-12406A and BE-12406B inhibited the growth of vincristine-resistant or doxorubicin-resistant P388 murine leukemia cell lines as well as their parent sensitive cell line. In in vivo experiments, BE-12406A inhibited the growth of S-180 murine ascites tumor.
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  • SHIGERU NAKAJIMA, KATSUHISA KOJIRI, HIROYUKI SUDA, MASANORI OKANISHI
    1991 Volume 44 Issue 10 Pages 1061-1064
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The structure of BE-12406A and BE-12406B, which were isolated from the culture broth of a streptomycete as antitumor substances, were determined by means of spectral analyses and chemical studies. The structure of BE-12406A is l-hydroxy-10-methoxy-8-methyl-12-α-L-rhamnopyranosyloxy-6H-benzo[d]naphtho[l, 2-b]pyran-6-one, and that of BE-12406B is l, 10-dihydroxy-8-methyl-12-α-L-rhamnopyranosyloxy-6H-benzo[d]naphtho[1, 2, 2-b]pyran-6-one.
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  • MUTSUO NAKAJIMA, KAZUKO ITOI, YASUYUKI TAKAMATSU, SADAO SATO, YOUJI FU ...
    1991 Volume 44 Issue 10 Pages 1065-1072
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Cornexistin, a new compound demonstrating promising herbicidal activity, was purified from the culture filtrate of a newly-isolated fungus identified as Paecilomyces variotii SANK 21086. The compound was extracted with organic solvents from the culture filtrate, purified using column chromatography on Sephadex LH-20 and finally crystallized from methylene chloride.
    Following analysis of its physico-chemical properties it was identified to be a new compound belonging to the nonadride group. Chemical structure elucidation was conducted by analyses of various spectral data and the structure was finally confirmed by means of X-ray crystallographic analysis. Based on its herbicidal characteristics cornexistin may be classified as a postemergence herbicide active against certain young annual and perennial monocotyledonous and dicotyledonous plants with selective protection for corn.
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  • WAN-JOO KIM, KWANG-YOUN KO, HONGBUM KIM, JONGHOON OH
    1991 Volume 44 Issue 10 Pages 1073-1082
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The synthesis, antibacterial activity and oral absorption of novel cephalosporins (3a-3d) having a 2-propenyl group at the C-3 position are described. Diphenylmethyl 7-amino-3-(2-propenyl)-3-cephem-4-carboxylate HCl (4) prepared from 7-aminocephalosporanic acid in 12 steps was acylated with various acid moieties to give cephems 3a-3d. The cephems 3a-3c showed similar antibacterial activities as cefixime. However, these cephems were not well absorbed orally.
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  • WAN-JOO KIM, KWANG-YOUN KO, MYUNG HEE JUNG, MOONHWAN KIM, KEY-IN LEE, ...
    1991 Volume 44 Issue 10 Pages 1083-1087
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Three prodrug esters (2a-2c) of 3-(2-propenyl)cephem (1a) have been prepared and their oral absorption was determined in rats and mice. While pivaloyloxymethyl ester (2a) did not improve the oral absorption of the parent cephem 1a, [(1-methyl)ethoxycarbonyloxy]ethyl ester (2b) and (5-methyl-2-oxo-1, 3-dioxolen-4-yl)methyl ester (2c) improved oral absorption by a factor of five.
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  • YOSHIKAZU ISHII, MASATAKA ICHIKAWA, KEIZO YAMAGUCHI, KUNIO TAKANO, MAT ...
    1991 Volume 44 Issue 10 Pages 1088-1095
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Enterobacter cloacae NUH10 was isolated at Nagasaki University Hospital in 1987. E. cloacae NUH10 is a mutant strain which produces high levels of cephalosporinase. E. cloacae ATCC 23355 is known to be sensitive to so-called third generation cephems and produces an inducible cephalosporinase.
    The polyclonal antibody to cephalosporinase extracted from E. cloacae NUH10 was utilized in post-embedding immunogold labeling in order to localize this protein in E. cloacae ATCC 23355 and E. cloacae NUH10. Immunocytochemical localization of the cephalosporinase in both strains was observed with and without incubation with an inducer. Cephalosporinase was detected in both the cytoplasm and periplasmic space of E. cloacae ATCC 23355 and E. cloacae NUH10 incubated in medium including cefoxitin as an inducer. In the case of incubation without the inducer, a small quantity of cephalosporinase was located in the periplasmic space in either strain of bacteria. Western blot analysis showed that cephalosporinase was predominantly localized in the periplasmic space rather than in the cytoplasmic space.
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  • M. S. KUO, D. A. YUREK, D. G. CHIRBY, J. I. CIALDELLA, V. P. MARSHALL
    1991 Volume 44 Issue 10 Pages 1096-1100
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Novobiocin was inactivated by Streptomyces niveus US 2094 in fermentation. The inactivation product was isolated and characterized by NMR and MS as 2"-O-carbamylnovobiocin. The MICs of novobiocin and 2"-O-carbamylnovobiocin were determined for S. niveus strains.
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  • KIYOHIRO NISHIKAWA, CHIEKO SHIBASAKI, MASAHARU HIRATSUKA, MASAYUKI ARA ...
    1991 Volume 44 Issue 10 Pages 1101-1109
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Antitumor activities of 15-deoxyspergualin (NKT-01), an analogue of spergualin (SGL), were examined in cultured tumor cells, transplantable murine tumors, and human tumor xenografts in nude mice. NKT-01 exhibited strong antitumor activity specifically against leukemias both in vitro and in vivo. Moreover, it also showed activity against AH66F hepatoma, M5076 fibrosarcoma and MH134 hepatoma. However, antitumor activity of NKT-01 against other non-leukemic tumors was marginal. Effective dose range of NKT-01 in sensitive tumors was so wide that the largest chemotherapeutic indexes were produced by NKT-01 in P388 and L1210 leukemias among 15 antitumor agents examined.
    The efficacy of NKT-01 against doxorubicin- and cytosine arabinoside-resistant P388 leukemias was comparable to that against parental sensitive P388 leukemia. NKT-01 also retained activity against other P388 leukemia sublines resistant to cisplatin, 5-fluorouracil or nimustine, although the effect was slightly decreased. In addition, in the in vitro and in vivo experiments using NKT-01-resistant P388 and SGL-resistant L1210(IMC) leukemias, no cross-resistance was observed. Moreover, collateral sensitivity was observed especially to alkylating agents in animal study.
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  • OSAMU JOHDO, TOMOYUKI ISHIKURA, AKIHIRO YOSHIMOTO, TOMIO TAKEUCHI
    1991 Volume 44 Issue 10 Pages 1110-1120
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Five mutant (or variant) strains producing new anthracycline antibiotics were derived from Streptomyces violaceus A262 by mutagenesis treatment. Strain SE1-625 showed a limited production of three known β-rhodomycinone diglycosides while the parent strain produced numerous unidentified β-rhodomycinone glycosides. Strain SU2-730 was an antibiotic-blocked mutant which produced only ε-rhodomycinone glycosides (named epelmycins). Strains SC-7 and SE2-2385 were variants which produced α-citromycinone glycosides (named yellamycins) and β-isorhodomycinone glycosides (named obelmycins), respectively. Strain SE2-2385-A1 produced α2-rhodomycinone glycosides (named alldimycins). Glycosidation-less mutants which accumulated only aglycone were also obtained. Isolation of these mutants or variants and preliminary identification of their anthracycline products are described.
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  • OSAMU JOHDO, YOSHIO WATANABE, TOMOYUKI ISHIKURA, AKIHIRO YOSHIMOTO, HI ...
    1991 Volume 44 Issue 10 Pages 1121-1129
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    New anthracycline antibiotics, identified as ε-rhodomycinone glycosides, were isolated from the culture broth of a blocked mutant of β-rhodomycin-producing Streptomyces violaceus A262. They were designated as epelmycins A, B, C, D and E, and assayed for their in vitro cytotoxicities against murine leukemic L1210 cell culture and the antimicrobial activities in comparison with known anthracycline antibiotics.
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  • OSAMU JOHDO, YOSHIO WATANABE, TOMOYUKI ISHIKURA, AKIHIRO YOSHIMOTO, HI ...
    1991 Volume 44 Issue 10 Pages 1130-1140
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    New anthracycline antibiotics, designated as obelmycins A, D, E, F and G, were isolated from the culture broth of a variant strain of β-rhodomycin-producing Streptomyces violaceus A262, identified as β-isorhodomycinone glycosides and γ-isorhodomycinone glycosides and assayed for their in vitro cytotoxicities against murine leukemic L1210 cell culture and the antimicrobial activities in comparison with some known anthracyclines.
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  • MARIA JESUS YEBRA, JESUS SANCHEZ, CRISTINA G. MARTIN, CARLOS HARDISSON ...
    1991 Volume 44 Issue 10 Pages 1141-1147
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    Sinefungin is an antibiotic structurally related to S-adenosylmethionine. It has been described as an inhibitor of RNA transmethylation reactions in viruses and eukaryotic organisms, but not in bacteria. We show here that sinefungin strongly inhibits RNA methyltransferase activity, but not the biosynthesis of these enzymes in Streptomyces. All the methylated bases found in Streptomyces RNA (1-methyladenine, N6-methyladenine, N6, N6-dimethyladenine and 7-methylguanine) are inhibited by this antibiotic. Experiments with sinefungin analogues show that specific changes in the ornithine radical of the molecule still preserve its inhibitory capability. The substitution of the adenine radical by uridine causes the loss of the inhibitory effect. These results and our former studies on Streptomyces DNA methylation, suggest that nucleic acid modification is the main target of sinefungin in Streptomyces.
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  • UWE GOTTSCHALK, MARTIN C. GARNETT, RACHEL K. WARD, AXEL MAIBÜCHER ...
    1991 Volume 44 Issue 10 Pages 1148-1154
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
    The pharmacokinetics of neocarzinostatin (NCS) have been compared to NCS conjugates with monoclonal antibodies using Balb/c and tumor bearing nude mice. Data on blood and whole body clearance revealed that the high MW conjugate persists in the body far longer and at a higher level than the free drug. Excretion of the free drug occurs with an extremely rapid renal clearance and localization of the remaining drug in the kidney, whereas the NCS immunoconjugate remained in circulation far longer allowing time for tumor localization to occur without renal accumulation of drug.
    In addition, NCS conjugated to monoclonal antibody was found to retain its activity in human serum better than free drug, in agreement with data obtained for other NCS-derivatives. Half-time of inactivation was greatly extended when measured under relevant conditions in a DNA strand-break assay.
    The results indicate that two of the most important requirements for the successful targeting of NCS in vivo, decreased clearance rate and increased serum stability are achieved by conjugation to antibody. Both results increase the probability of NCS accumulating in tissue while still in its active form.
    Coupling of NCS to monoclonal antibody decreases clearance and inactivation rate and increases localization of the active drug in tumor tissue.
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  • OSAMU JOHDO, HIROSHI TONE, ROKURO OKAMOTO, AKIHIRO YOSHIMOTO, HIROSHI ...
    1991 Volume 44 Issue 10 Pages 1155-1159
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • OSAMU JOHDO, HIROSHI TONE, ROKURO OKAMOTO, AKIHIRO YOSHIMOTO, HIROSHI ...
    1991 Volume 44 Issue 10 Pages 1160-1164
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • OSAMU ANDO, HITOMI SATAKE, KAZUKO ITOI, AKIRA SATO, MUTSUO NAKAJIMA, S ...
    1991 Volume 44 Issue 10 Pages 1165-1168
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • STEPHEN CONNOLLY, KEVIN W. MOORE, MICHAEL D. COOKE, JOHN G. WALMSLEY, ...
    1991 Volume 44 Issue 10 Pages 1169-1171
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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  • JAMES M. BALKOVEC, MICHAEL J. SZYMONIFKA, JAMES V. HECK, RONALD W. RAT ...
    1991 Volume 44 Issue 10 Pages 1172-1177
    Published: October 25, 1991
    Released: April 19, 2006
    JOURNALS FREE ACCESS
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