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ISOLATION, STRUCTURE DETERMINATION, AND BIOSYNTHESIS
WILLIAM L. RUSSELL, RAMESH C. PANDEY, CARL P. SCHAFFNER, HENRY M. FALE ...
1988 Volume 41 Issue 2 Pages
149-156
Published: February 25, 1988
Released on J-STAGE: April 19, 2006
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Micromonospora purpureochromogenes subsp,
halotolerans was found to produce crisarnicin C, a novel antibiotic, together with crisamicin A. Crisamicin C was purified by silica gel column chromatography and its physico-chemical properties, structure and biosynthesis were studied. Crisamicin C, mp 260°C (dec), showed UV maxima at 392 (ε 9, 497), 261 (ε 32, 959) and 232 nm (ε 24, 623) in CH
3CN, and gave an IR spectrum with absorbances at 1782 (lactone), 1705 and 1655 (quinone) cm
-1. Crisamicin C plasma desorption mass spectrornetry (PD-MS) m/z 615.9 ((M+H)
+, hydroquinone) was 16 amu higher than crisamicin A PD-MS m/z 600 ((M+H)
+, hydroquinone) suggesting that the two antibiotics differ by one additional oxygen in crisamicin C. Analysis of
1H and
13C NMR spectra, in comparison with those of crisamicin A, indicated that crisamicin C was the 4'a, 10'a epoxide derivative of crisamicin A. Carbon-thirteen labeled acetate feeding experiments were used to confirm the positions of the epoxide and other structural features. Crisamicin C was a more potent antibiotic than crisamicin A, but shared the same spectrum of antimicrobial activity (Grampositive only).
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A. D. ARGOUDELIS, L. BACZYNSKYJ, W. J. HAAK, W. M. KNOLL, S. A. MIZSAK ...
1988 Volume 41 Issue 2 Pages
157-169
Published: February 25, 1988
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Paulomycin A
2 (C
34H
46N
2O
17S), paulomycin C (C
32H
42N
2O
17S), paulomycin D (C
31H
40N
2O
17S), paulomycin E (C
29H
36N
2O
16S) and paulomycin F (C
29H
38N
2O
16S) have been isolated from fermentations of
Streptomyces paulus strain 273. The structure of these compounds was determined using NMR and mass spectroscopic techniques. The new paulomycins, like paulomycins A and B (J. Antibiotics 35: 285-294, 1982) are highly active mainly against Gram-positive organisms.
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I. SYNTHESIS, ANTIBACTERIAL ACTIVITY AND ORAL ABSORPTION OF NEW 3-(O-SUBSTITUTED)-7β-[D-α-AMINO-α-(4-HYDROXYPHENYL)ACETAMIDO]CEPHALOSPORINS
CHIHIRO YOKOO, MASAMI GOI, AKIRA ONODERA, MITSUO MURATA, TAKATOSHI NAG ...
1988 Volume 41 Issue 2 Pages
170-180
Published: February 25, 1988
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The synthesis, antibacterial activity and oral absorption of new 7β-[D-α-amino-α-(4-hydroxyphenyl)acetamido]cephalosporins (
1) with various O-substituents at the C-3 position of a cephalosporin nucleus are described. Of these, the cephalosporins (
1b-1e) having an alkoxycarbonylmethoxy group at the C-3 position showed good oral absorption in rats as well as potent activity against Gram-positive bacteria. The structure-activity relationships of
1 are also presented.
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II. SYNTHESIS, ANTIBACTERIAL ACTIVITY AND ORAL ABSORPTION OF 3-ALKOXYCARBONYLMETHOXY-7β-[(Z)-2-(2-AMINOTHIAZOL-4-YL)-2-(O-SUBSTITUTED OXYIMINO)-ACETAMIDO]CEPHALOSPORINS
CHIHIRO YOKOO, MASAMI GOI, AKIRA ONODERA, MITSUO MURATA, TAKATOSHI NAG ...
1988 Volume 41 Issue 2 Pages
181-192
Published: February 25, 1988
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The synthesis, antibacterial activity and oral absorption in rats of 3-alkoxycarbonylmethoxy-7β-[(
Z)-2-(2-aminothiazol-4-yl)-2-(
O-substituted oxyimino)acetamido]cephalosporins (
1) are described. In this cephalosporin series, 7β-[(
Z)-2-(2-aminothiazol-4-yl)-2-(carboxymethoxyimino)acetamido]cephalosporins (
Ib,
1i and
1j) with a lower alkoxycarbonylmethoxy group at the C-3 position of a cephem nucleus exhibited not only potent activity against Gram-negative bacteria but also good oral absorption in rats. Structure-activity relationships of
1 are also presented.
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BARBARA STEFANSKA, MARIA DZIEDUSZYCKA, MARIA BONTEMPS-GRACZ, EDWARD BO ...
1988 Volume 41 Issue 2 Pages
193-198
Published: February 25, 1988
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Eleven
N-enamine derivatives of daunorubicin and of its 5-imino analogue as well as of doxorubicin have been synthesized and evaluated for antileukemic activity
in vitro and
in vivo. Comparison of biological activities of examined compounds with other enamine derivatives of daunorubicin, reported earlier by us, has indicated that the optimal activity is shown by
N-(1-carboethoxypropen-1-yl-2)daunorubicin.
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PETER D. SENTER, DAVID R. LANGLEY, WALTER E. MANGER, DOLATRAI M. VYAS
1988 Volume 41 Issue 2 Pages
199-201
Published: February 25, 1988
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7-Cysteaminomitosane (RR-150) has been reported to be superior to mitomycin C against P388 leukemia and B-16 melanoma in mice and is less leukopenic. Studies reported here indicated the absence of a free thiol group in RR-150 and therefore the structure was incorrectly assigned. Reaction of mitomycin A. with either 2-aminoethanethiol or cystamine gave the same disulfide, 7-
N, 7'-
N'-dithiodiethylenedimitomycin C, which is the newly proposed structure for RR-150. Attempts to produce 7-cysteaminomitosane by reduction of the disulfide have not succeeded because of its apparent instability.
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JILL BARBER, JOHN A. CARVER, REUBEN LEBERMAN, GRAHAM M. V. TEBB
1988 Volume 41 Issue 2 Pages
202-206
Published: February 25, 1988
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The binding of the antibiotic kirromycin (mocimycin) to its target protein, bacteriadelongation factor Tu (EF-Tu), has been studied by
1H NMR spectroscopy using deuterated protein. Narrow lines were observed in the spectrum of the unbound protein (due to residual protons) and in the spectrum of the kirromycin-EF-Tu complex. The spectrum of the complex has been compared with the spectra of the unbound protein and the unbound drug, and the results are interpreted in terms of the mode of antibiotic action of kirromycin.
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MARIE-LAURE HOURDOU, FRANÇHISE BESSON, GEORGES MICHEL
1988 Volume 41 Issue 2 Pages
207-211
Published: February 25, 1988
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The biosynthesis of the β-amino acid components of iturins A was studied in comparison to the biosynthesis of fatty acids. Palmitic acid was incorporated into the lipid moiety of iturins A when it was added to the culture medium of the iturin producer
Bacillus subtilis. Addition of unlabeled palmitic acid enhanced the formation of straight-chain β-amino acids and addition of valine or leucine increased the production of branched β-amino acids. These mod fications correlated with modifications in the corresponding biosynthesized fatty acids.
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BERNARD FABRE, ELISE ARMAU, GILLES ETIENNE, FRÉDÉRIC LEG ...
1988 Volume 41 Issue 2 Pages
212-219
Published: February 25, 1988
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A simple and selective assay system was developed in the search for new insecticidal substances from
Actinomycetales strains propagated on solid culture media. The strains were first tested for their ability to produce antimicrobial compounds. Only strains displaying weak or no activity were retained and screened in the insecticidal bioassay. Microbial solid cultures were given as food to larvae and to adults of
Musca domestica to detect insecticide producers. A second phase, after extraction of the active compounds, consisted of an evaluation of the insecticidal potency and a primarily biological identification of the products synthesized by the selected strain.
Of 6, 280 actinomycete strains which were screened, 47 were active but only 30 of these were finally chosen in the second phase of screening. All these strains, except one, produced known metabolites such as piericidins, avermectins or valinomycin. The one strain, CL307-24, and its insecticide products appeared novel and will be the topic of further study.
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TETSUSHI SAINO, TETSUYA SOMENO, SHIN-ICHI ISHII, TAKAAKI AOYAGI, HAMAO ...
1988 Volume 41 Issue 2 Pages
220-225
Published: February 25, 1988
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Thirty analogues of leupeptin were synthesized and examined for their inhibitory activities against trypsin, papain, plasmin, kallikrein, thrombin and urokinase
in vitro. Benzoyland α-naphthalenesulfonyl-L-leucyl-L-argininal were 8 times more inhibitory to papain, benzyloxycarbonyl-L-pyroglutamyl-L-leucyl-L-argininal 10 times more to trypsin and plasmin, and DL-2-pipecolyl-L-leucyl-L-argininal 25 times more to kallikrein than leupeptin. Against urokinase, only L-pyroglutamyl-L-leucyl-L-argininal exhibited a potent inhibitory activity. α-Naphthalenesulfonyl-, dansyl- and benzyloxycarbonyl-(2
S, 3
R)-3-ammo-2-hydroxy-4-phenylbutyryl-L-leucyl-L-argininal were inhibitory to thrombin.
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HIROYUKI ANZAI, YOICHI KUMADA, OSAMU HARA, TAKESHI MURAKAMI, REIKO ITO ...
1988 Volume 41 Issue 2 Pages
226-233
Published: February 25, 1988
Released on J-STAGE: April 19, 2006
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We have developed a method for gene replacement in
Streptomyces hygroscopicus which permits introduction of an
in vitro derived mutation carried on a plasmid into the chromosome. We constructed the plasmid pMSB212 which can replicate in
S. hygroscopicus and contains the step5 gene of the bialaphos biosynthetic pathway which was inactivated by a frame-shift mutation caused by filling in the cohesive ends of the
EcoR I site in the structural gene. pMSB212 was introduced into a bialaphos producer strain and by protoplast regeneration of the primary thiostrepton-resistant transformants, non-producing mutants, were obtained. Biochemical and genetical analyses indicated that these mutants were specifically blocked by introduction of the frame-shift mutation in the step5 gene on the chromosome. This method will enable us to obtain isogenic mutants of known genes and to identify new genes encoded on a cloned fragment.
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HIROSHI KURAMOCHI, MASAHARU HIRATSUKA, SAKIKO NAGAMINE, KATSUTOSHI TAK ...
1988 Volume 41 Issue 2 Pages
234-238
Published: February 25, 1988
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The amine oxidase activities contained in calf serum and human serum were detected at levels of 90.8 and less than 0.1 nmol O
2/minute/ml serum, respectively, by measuring oxygen consumption coupled with spermidine oxidation. Deoxyspergualin (NKT-01) and spergualin (SGL) containing spermidine in their structure were also oxidized in calf serum at the rate of 3.6 and 11.6 nmol O
2/minute/ml serum, respectively. To investigate whether amine oxidase is essential for NKT-01 and SGL to exhibit their antiproliferative activities or not, the
in vitro activities of NKT-01, SGL and polyamines against LI210 cells were examined in the presence of calf or human serum. Polyamines exhibited antiproliferative activity only in the presence of calf serum, while NKT-01 and SGL inhibited cell growth in the presence of both calf and human serum. In the presence of calf serum the activity of NKT-01 was inhibited by aminoguanidine, an amine oxidase inhibitor. Aminoguanidine did not inhibit the activity of NKT-01 in the presence of human serum. The activity of NKT-01 was shown at much lower concentrations in the presence of human serum than that in the presence of calf serum, and was strongly dependent on incubation time. The
in vivo activities of NKT-01, SGL and SGL derivatives correlated with their
in vitro activities in the presence of human serum. These results suggest that the
in vivo antitumor activities of NKT-01, SGL and SGL derivatives may be attributed to a mechanism different from those of amine oxidase-oxidized product and represent a novel growth inhibitory action.
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SATOSHI OKUNO, ISAO MAEZAWA, YOSHIMITSU SAKUMA, TADAHIRO MATSUSHITA, T ...
1988 Volume 41 Issue 2 Pages
239-246
Published: February 25, 1988
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The serum concentrations, urinary and biliary excretions of six penicillin derivatives including aspoxicillin (ASPC) were studied in rats and the correlation between the values of pharmacokinetic parameters thus obtained and the Rm values measured by means of reversed phase TLC were analyzed.
Among the penicillins studied, the hydrophilicity of amoxicillin was the highest (the lowest Rm value), which was followed by those of ASPC, ampicillin,
p-hydroxypiperacillin, dehydroxyaspoxicillin and piperacillin in descending order. These Rm values were then correlated with the AUC values at 20 mg/kg of dosing, giving the results that more hydrophilic penicillins having a hydroxyl group show higher serum concentrations as well as greater AUC values. The studies of correlation between the Rm values and the urinary or biliary excretion revealed that hydrophilic penicillins were almost excreted into urine, but more hydrophobic ones were mainly eliminated into bile.
From the above results, a hydroxyl group introduced to the phenyl group of ASPC was considered to have a role that increases the hydrophilicity of ASPC, giving higher and longer persistency of the serum levels and increasing the excretion of drugs into urine.
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HIROSHI TOMODA, HIDETOSHI KUMAGAI, YOKO TAKAHASHI, YOSHITAKE TANAKA, Y ...
1988 Volume 41 Issue 2 Pages
247-249
Published: February 25, 1988
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KAZUHIKO OTOGURO, AKIRA NAKAGAWA, SATOSHI OMURA
1988 Volume 41 Issue 2 Pages
250-252
Published: February 25, 1988
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A. L. LABORDE, J. I. CIALDELLA, F. B. SHILLIDAY, V. P. MARSHALL
1988 Volume 41 Issue 2 Pages
253-254
Published: February 25, 1988
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C. HÖNLINGER, W. A. HAMPEL, M. RÖHR, C. P. KUBICEK
1988 Volume 41 Issue 2 Pages
255-257
Published: February 25, 1988
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YOSHITAKE TANAKA, KEIKO KIMURA, YASUKO KOMAGATA, KAZUO TSUZUKI, HIROSH ...
1988 Volume 41 Issue 2 Pages
258-260
Published: February 25, 1988
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AKIRA OKURA, MASAAKI ISHIZUKA, TOMIO TAKEUCHI
1988 Volume 41 Issue 2 Pages
261-263
Published: February 25, 1988
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NAN-JIN WANG, YUAN FU, GUI-HUA YAN, GUANG-HONG BAO, CHANG-FU XU, CUN-H ...
1988 Volume 41 Issue 2 Pages
264-267
Published: February 25, 1988
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YAEKO KONDA, AKIRA NAKAGAWA, YOSHIHIRO HARIGAYA, MASAYUKI ONDA, ROKURO ...
1988 Volume 41 Issue 2 Pages
268-270
Published: February 25, 1988
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TOYOSHIGE ENDO, KAORI KOBAYASHI, NAOHIRO NAKAYAMA, TERUO TANAKA, TAKAS ...
1988 Volume 41 Issue 2 Pages
271-273
Published: February 25, 1988
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