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SUSUMU TOHMA, HARUO KONDO, JUNKO YOKOTSUKA, JUNJI IWAMOTO, GEN MATSUHA ...
1989 Volume 42 Issue 8 Pages
1205-1212
Published: August 25, 1989
Released on J-STAGE: April 19, 2006
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Detailed analysis of the fermentation broth of
Streptomyces griseus strain FT3-4 resulted in the identification of two new streptomycin analogues named ashimycins A and B. Their structures have been determined by NMR spectral analysis and chemical degradations.
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JOHN P. DIRLAM, ANNETTE M. BELTON, SHANG-POA CHANG, WALTER P. CULLEN, ...
1989 Volume 42 Issue 8 Pages
1213-1220
Published: August 25, 1989
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A new monocarboxylic acid ionophore antibiotic related to zincophorin, CP-78, 545 (
1). was found in the culture broth of
Streptomyces sp. N731-45. CP-78, 545 was extracted with organic solvents and purified by column chromatography. The metabolite, which is active
in vitro against certain Gram-positive bacteria, as well as the anaerobe
Treponema hyodysenteriae, and a coccidium
Eimeria tenella, was isolated as a water insoluble magnesium salt (
2) in 2:1 (ligand/metal) stoichiometry. The structure of CP-78, 545 was elucidated by spectroscopic (NMR and MS) methods, and the relative stereochemistry was determined by single-crystal X-ray analysis of the cadmium salt (
3). CP-78, 545,
i.e., 24-dehydrozincophorin, is unique since its molecular backbone contains a terminal double bond previously not found in other polyether ionophores.
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I. TAXONOMY, FERMENTATION, ISOLATION, PHYSICO-CHEMICAL CHARACTERISTICS
OSAMU NAKAYAMA, MASASHI YAGI, MIHO TANAKA, SUMIO KIYOTO, MASAKUNI OKUH ...
1989 Volume 42 Issue 8 Pages
1221-1229
Published: August 25, 1989
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WS-9659 A and B, produced by
Streptomyces sp. No. 9659, were extracted from cultured broth, purified by solvent extraction followed by chromatography on silica gel and then isolated as prisms (C
22H
24N
2O, mp 161-162°C, C
22H
23N
2OCl, mp 152-153°C). WS-9659 A and B have testosterone 5α-reductase inhibitory activity. The IC
50 values of WS-9659 A and B for partially purified rat prostate testosterone 5α-reductase were 5.0 × 10
-7 M and l.0× 10
-5 M, respectively.
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II. STRUCTURAL ELUCIDATION OF WS-9659 A AND B
OSAMU NAKAYAMA, NOBUHARU SHIGEMATSU, AKIRA KATAYAMA, SHIGEHIRO TAKASE, ...
1989 Volume 42 Issue 8 Pages
1230-1234
Published: August 25, 1989
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On the basis of spectroscopic and chemical evidence, the structures of WS-9659 A and B isolated as inhibitors of testosterone 5α-reductase from a
Streptomyces have been established as
1 and
2, respectively. The reductase inhibitory activities of the derivatives
5 and
6, and degradation products
3 and
8 were considerably less active and substantially inactive, respectively.
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III. BIOLOGICAL CHARACTERISTICS AND PHARMACOLOGICAL CHARACTERISTICS
OSAMU NAKAYAMA, HIROYUKI ARAKAWA, MASASHI YAGI, MIHO TANAKA, SUMIO KIY ...
1989 Volume 42 Issue 8 Pages
1235-1240
Published: August 25, 1989
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WS-9659 A, a novel phenazine, produced by a
Streptomyces sp., had testosterone 5α-reductase inhibition activity on rat, dog and human prostates. However, WS-9659 A did not show any inhibitory activities for aldose reductase on rabbit lenses and lactate dehydrogenase on pig hearts. WS-9659 A was a competitive inhibitor against testosterone 5α-reductase on rat prostates by use of testosterone as a substrate. Radio receptor binding assay of androgen receptor of rat prostates revealed that WS-9659 A had no affinity for this receptor.
WS-9659 A was tested subcutaneously in immature castrated rats to confirm its effect on the growth of the ventral prostates induced by testosterone propionate.
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II. DERIVATIVES SUBSTITUTED AT N(4) OF THE PIPERAZINE RING
FRANK P. HARRINGTON, SARAH J. KNOTT, PETER J. O'HANLON, ROBERT SOUTHGA ...
1989 Volume 42 Issue 8 Pages
1241-1247
Published: August 25, 1989
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The structure-activity relationships within a series of penicillins and cephalosporins containing an N(4)-substituted piperazine-2, 3-dione moiety in the C(6)/C(7)-β-side chain are discussed.
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JENNIFER B. K. NIELSEN, BYRON H. ARISON
1989 Volume 42 Issue 8 Pages
1248-1252
Published: August 25, 1989
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3-Methylpseudouridine (β isomer) has been identified in fermentation broths of
Nocardia lactamdurans. It accumulates at quite high levels following the accumulation of extracellular uracil in strains exhibiting increased levels of
de novo pyrimidine biosynthetic enzymes. It is labeled by exogenous uracil, and appears to result from an irreversible modification of one of the components of the elevated pyrimidine pool. Its methyl group is labeled efficiently by [
methyl-
14C]methionine.
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MANUEL DEBONO, KEVIN E. WILLARD, HERBERT A. KIRST, JULIE A. WIND, GARY ...
1989 Volume 42 Issue 8 Pages
1253-1267
Published: August 25, 1989
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A series of 20-deoxo-20-cyclic (alkylamino) derivatives of tylosin, desmycosin, macrocin and lactenocin was prepared by reductive amination of the C-20 aldehyde group. The majority of the compounds were prepared using metal hydrides (sodium cyanoborohydride or sodium borohydride) as the reducing agents and a suitable cyclic alkylamine. Subsequently, a more convenient procedure was developed using formic acid as a reducing agent. The C-20 amino derivatives prepared from desmycosin exhibited good
in vitro antimicrobial activity against
Pasteurella haemolytica and
Pasteurella multocida (MIC range of 0.78-6.25μg/ml) as well as
Mycoplasma species (MIC range of 0.39 - 6.25 μg/ml). Several derivatives showed excellent oral efficacy against infections caused by
P. multocida in chicks, One of these derivatives, 20-deoxo-20-(3, 5-dimethylpiperidin-1-yl)desmycosin (tilmicosin or EL-870) was selected for development as a therapeutic agent for pasteurellosis in calves and pigs.
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I. SYNTHESIS AND BIOLOGICAL ACTIVITY
ALDO TRANI, PIETRO FERRARI, ROSETTA PALLANZA, ROMEO CIABATTI
1989 Volume 42 Issue 8 Pages
1268-1275
Published: August 25, 1989
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A series of thiourea and isothiouronium salt derivatives of the aglycone of teicoplanin was prepared by reaction of the terminal amino group with isothiocyanates, followed by
S-alkylation of the thiourea compounds.
Unexpectedly, the two classes of derivatives show a similar
in vitro antibacterial activity against Gram-positive bacteria.
Thiourea compounds, due to the lack of a positively charged
N-terminus group, have a 10-fold lower binding constant to Ac-D-Ala-D-Ala, a bacterial cell-wall model, than the parent antibiotic and isothiouronium salt derivatives.
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II. REACTION MECHANISM AND BIOLOGICAL ACTIVITY
ALDO TRANI, PIETRO FERRARI, ROSETTA PALLANZA, ROMEO CIABATTI
1989 Volume 42 Issue 8 Pages
1276-1282
Published: August 25, 1989
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N
15-Isothiouronium derivatives of teicoplanin and its aglycone submitted to alkaline condition give rise to an intramolecular cyclization. The structures of the new γ-lactam derivatives were determined by using
1H NMR, IR and fast atom bombardment mass spectra. The cyclization mechanism was interpreted on the basis of the identification of the intermediate structure.
The poor
in vitro antibacterial activity of the new cyclic compounds and the negligible affinity for the synthetic peptidoglycan model Ac
2-L-Lys-D-Ala-D-Ala is probably due to the lack of the N-17 amidic proton and to the lack of the basic character of the nitrogen in position 15.
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ALFONS LAWEN, RENÉ TRADER, DIETER GEYL, RAINER ZOCHER, HORST KL ...
1989 Volume 42 Issue 8 Pages
1283-1289
Published: August 25, 1989
Released on J-STAGE: April 19, 2006
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An enzyme preparation, isolated from extracts of the fungus
Beauveria nivea (previously designated
Tolypocladium inflatum), is able to synthesize cyclosporins (Cy's)
in vitro. At suboptimal temperature it was possible to yield about 50 μg of CyA per ml. The enzyme also produces several of the naturally occuring congeners of CyA, such as the Cy's B, C, D, G, M, O, Q, U and V and some of the analogues known to be produced by the fungus
via precursor directed biosynthesis, like dihydro-CyA, [
N-methyl-L-β-cyclohexylalanine
1]CyA, [1-allylglycine
2]CyA and [D-serine
8]CyA.
Furthermore, Cy's not obtainable by the fungus could be prepared by the enzyme system in the presence of the appropriate precursor amino acids; the synthesis of [
N-methyl(+)-2-amino-3-hydroxy-4, 4-dimethyloctanoic acid
1]CyA, [1-norvaline
2, 5,
N-methyl-L-norvaline
11]CyA, [L-norvaline
5,
N-methyl-L-norvaline
11]CyA, [L-
allo-isoleucine
5,
N-methyl-L-
allo-isoleucine
11]CyA; [L-
allo-isoleucine
5, 11]CyA, [D-2-aminobutyric acid
8]CyA and [β-chloro-D-alanine
8]CyA could be established.
The immunosuppressive effects of the new derivatives are discussed.
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JUNJI MAGAE, HIROYUKI OSADA, KAZUO NAGAI, MAKARI YAMASAKI, KIYOSHI ISO ...
1989 Volume 42 Issue 8 Pages
1290-1293
Published: August 25, 1989
Released on J-STAGE: April 19, 2006
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The effect of tautomycin (TM) on protein kinase C (PKC) was studied in a cell-free system. TM, like phorbol dibutyrate (PDBu), enhanced both base-line and Ca
2+/phospholipidsdependent protein kinase activity. However, PDBu but not TM increased the affinity of the enzyme for calcium ions (Ca
2+), suggesting that TM is a new activator of PKC, distinct from PDBu. In the presence of 10 μg/ml phosphatidyl inositol, the activity of PKC reached maximum at 10
-3 M Ca
2+ concentration when the other co-factors were absent. Both TM and PDBu increased the maximum level of PKC activity at the optimum concentration of Ca
2+, suggesting that they interacted with the site of PKC which is distinct from the site where Ca
2+ interacts. TM and PDBu did not activate the enzyme when protamine sulfate in place of histone III-S was used as a substrate, indicating that they activate PKC by affecting the regulatory domain of the enzyme.
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III. ANTITUMOR ACTIVITY
YONG-SU ZHEN, XIU-YING MING, BIN YU, TOSHIO OTANI, HITOSHI SAITO, YUJI ...
1989 Volume 42 Issue 8 Pages
1294-1298
Published: August 25, 1989
Released on J-STAGE: April 19, 2006
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C-1027, a new macromolecular antitumor antibiotic produced by
Streptomyces globisporus C-1027, showed extremely potent cytotoxicity toward cultured cancer cells. Compared in terms of IC
50 values, antibiotic C-1027 showed much more potent cytotoxicity than doxorubicin, mitomycin C and neocarzinostatin. Spermatogonial assay, a prescreen for anticancer drugs, was highly sensitive for detection of C-1027. At tolerable doses, C-1027 exhibited marked inhibition on a panel of transplantable tumors in mice, which included leukemia L1210, P388, ascites hepatoma H22, sarcoma 180 and melanoma Harding-Passey.
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TATSUHIRO OGAWA, MICHIO ICHIMURA, SHIGEO KATSUMATA, MAKOTO MORIMOTO, K ...
1989 Volume 42 Issue 8 Pages
1299-1301
Published: August 25, 1989
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TADASHI FURUMOTO, NAOKI ASANO, YUKIHIKO KAMEDA, KATSUHIKO MATSUI
1989 Volume 42 Issue 8 Pages
1302-1303
Published: August 25, 1989
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TIMOTHY A. BLIZZARD, CAROLYN L. RUBY, HELMUT MROZIK, FRANZ A. PREISER, ...
1989 Volume 42 Issue 8 Pages
1304-1307
Published: August 25, 1989
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YUKIHIRO NISHIYAMA, NAOHIKO YAMAMOTO, YOSHINARI YAMADA, HISASHI FUJIOK ...
1989 Volume 42 Issue 8 Pages
1308-1311
Published: August 25, 1989
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KIMIE KOBINATA, HIROO KUSAKABE, TOSHIYUKI SHIMIZU, ISAMU YAMAGUCHI, KI ...
1989 Volume 42 Issue 8 Pages
1312-1314
Published: August 25, 1989
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YASUSHI TAKAGI, HAE-IL PARK, TSUTOMU TSUCHIYA, SUMIO UMEZAWA, TOMIO TA ...
1989 Volume 42 Issue 8 Pages
1315-1317
Published: August 25, 1989
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YASUSHI TAKAGI, NAOKI KOBAYASHI, TSUTOMU TSUCHIYA, SUMIO UMEZAWA, TOMI ...
1989 Volume 42 Issue 8 Pages
1318-1320
Published: August 25, 1989
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HARUMITSU IMAI, AKIRA NAKAGAWA, SATOSHI OMURA
1989 Volume 42 Issue 8 Pages
1321-1323
Published: August 25, 1989
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AKIRA NAKAGAWA, SATOMI MIURA, HARUMITSU IMAI, NOBUTAKA IMAMURA, SATOSH ...
1989 Volume 42 Issue 8 Pages
1324-1327
Published: August 25, 1989
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MICHAEL J. BASKER, COLIN H. FRYDRYCH, FRANK P. HARRINGTON, PETER H. MI ...
1989 Volume 42 Issue 8 Pages
1328-1330
Published: August 25, 1989
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