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ARNOLD L. DEMAIN
2000 Volume 53 Issue 10 Pages
995-1002
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Today much is known about the biology of penicillin and cephalosporin production by fungi including the pathways, the biosynthetic enzymes including some crystal structures, the genes and their cloning, expression, sequencing and chromosomal locations, the regulation of the genes and enzymes and even some intelligent guesses about their evolutionary relationships. The key breakthrough that led to rapid progress in these areas was the subcellular work done by EDWARD P. ABRAHAM and his Oxford colleagues in the early 1970s. With his advice and encouragement, my laboratory was able to prepare reliably active soluble cell-free preparations which were instrumental in elucidation of the biosynthetic pathways in fungi (and also in bacteria) by laboratories throughout the world.
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JEREMY M. T. HAMILTON-MILLER
2000 Volume 53 Issue 10 Pages
1003-1007
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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From ABRAHAM'S Discoveries to Novel Concepts of Non-Ribosomal Peptide Synthesis
JUAN F. MARTIN
2000 Volume 53 Issue 10 Pages
1008-1021
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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The tripeptide δ-(L-α-aminoadipyl)-L-cysteinyl-D-valine (ACV) was discovered by ARNSTEIN and MORRIS in
Penicillium chrysogenum and ABRAHAM and coworkers in
Acremonium chrysogenum. Other analogous tripeptides and tetrapeptides were later reported in these and other β-lactam producing fungi and actinomycetes. The ACV tripeptide is synthesized by a large non-ribosomal peptide synthetase named ACV synthetase encoded by the 11 kb
pcbAE gene. This gene has been cloned from the DNA of four different filamentous fungi and two actinomycetes. Detailed analysis of the multifunctional ACV synthetases reveals that they consist of three repeated modules (initially named domains) involved in activation of the corresponding amino acids L-α-aminoadipic acid, L-cysteine and L-valine. Each module consists of functional domains for amino acid activation (A), condensation (C) and thiolation (T). In addition the last module of the ACV synthetase contains an epimerization domain (E) involved in conversion of the L-valine to its D-isomer when the tripeptide is still enzyme linked. There are seven epimerization motifs conserved in the third module of all ACV synthetases. In addition, there is an integrated thioesterase domain in the
C-terminal region of the ACV synthetases that appears to be involved in the selective release of the tripeptide with the correct LLD configuration. The structure of the ACV synthetase is similar to that of other modular non-ribosomal peptide synthetases of bacterial and fungal origin. This molecular knowledge opens the way for engineering novel tripeptide synthetases that may result in new bioactive compounds.
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DASANTILA GOLEMI, LAURENT MAVEYRAUD, AKIHIRO ISHIWATA, SAMUEL TRAMER, ...
2000 Volume 53 Issue 10 Pages
1022-1027
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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6-(Hydroxyalkyl)penicillanates have proven helpful as probes for the mechanisms of β-lactamases, enzymes of resistance for β-lactam antibiotics. The present report summarizes the concepts on design, syntheses and use of these molecules in mechanistic studies of β-lactamases.
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ANDRÉ BRYSKIER
2000 Volume 53 Issue 10 Pages
1028-1037
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Since 1964, seven waves of parenteral cephems have been reported. All of them were designed to meet medical needs. The first (group I) and the third (group III) waves were very successful and drugs belonging to group III are widely used in the treatment of severe infections. A new series of compounds (group VII), with a new compound underdevelopment was designed for the treatment of
Staphylococcus aureus strain resistant to methicillin but also to glyco- and lipoglycopeptides. By modifying the substituent at position 3 and 7 of the cephems rings optimal moieties have been fixed leading to potent anti-Gram-positive drugs.
Alterations of substituents are still in progress to obtain optimal anti-Gram-positive (anti-MRSA) compounds.
The first oral cephem cephalexin was introduced in clinical practice in 1967. Since this time, many esterified and non-esterified cephems have been synthesized and introduced in clinics. There are two groups of compounds, α-amino and non-α-amino cephems which are classified in six groups according to their chemical structure. The absorption route was explored, and three transporting systems have been described according to the physicochemical properties of these compounds, in addition prodrugs are passively absorbed.
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A. K. GANGULY
2000 Volume 53 Issue 10 Pages
1038-1044
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Ziracin is produced by
Micromonospora carbonacea1) and is highly active against Grampositive bacteria. In particular it is highly active against methicillin resistant staphylococci and vancomycin resistant enterococci. Ziracin, C
70H
97NO
38Cl
2, contains two orthoester linkages, a nitro sugar, a methylene dioxy group, two aromatic ester residues and thirty five centres of assymmetries. In this paper a brief description of the structural elucidation of ziracin is presented along with the chemical modification of the antibiotic which has led to the identification of several potent antibacterials.
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T. W. GLINKA, A. CHO, Z. J. ZHANG, M. LUDWIKOW, D. GRIFFITH, K. Hum, S ...
2000 Volume 53 Issue 10 Pages
1045-1052
Published: October 25, 2000
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SAR studies in a series of 3-heteroarylthio substituted cephalosporins established that high activity against methicillin-resistant
Staphylococcus aureus (MRSA) can be achieved with various heteroaryl substituents. Early results showed that highly lipophilic 3-heteroarylthio substituents, which were necessary for anti-MRSA activity, caused high affinity of such cephems toward serum proteins. Our earlier published efforts described discovery of zwitterionic cephems MC-02, 331 and RWJ-54428 (MC-02, 479), where serum binding was reduced by employing basic, positively charged functionalities attached to the 3-heteroarylthio substituent. In order to avoid low solubility problems associated with most such zwitterionic cephalosporins a wide variety of non-basic heteroaryl substituents was tested (non-zwitterionic cephems are more easily formulated as water soluble sodium salts for intravenous administration). Considerable reduction in serum binding was obtained in some analogs while maintaining high anti-MRSA potency.
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TOMOYASU ISHIKAWA, YIJJI IIZAWA, KENJI OKONOGI, AKIO MIYAKE
2000 Volume 53 Issue 10 Pages
1053-1070
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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In order to improve the antibacterial activity of cefozopran (CZOP) against methicillin-resistant
Staphylococcus aureus (MRSA), we initiated chemical modification to introduce a 2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(
Z)-hydroxyimino acetyl group at the C-7 position and a 3- or 6-substituted imidazo[1, 2-
b]pyridazinium or 5-substituted imidazo[1, 2-
a]pyridmium group at the C-3' position. Although this approach successfully enhanced the anti-MRSA activity of CZOP two to eight times, a slight decrease in the activity against Gram-negative bacteria including
Pseudomonas aeruginosa was involved. Among the novel derivatives, 3-(6-aminoimidazo[1, 2-
b]pyridazinium-1-yl)methyl-7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(
Z)-hydroxyiminoacetamido]-3-cephem-4-carboxylate (
44a) showed an excellent balance of activity against MRSA and Gram-negative bacteria.
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TOMOYASU ISHIKAWA, KJEIJI KAMIYAMA, NOBUYUKI MATSUNAGA, HIROYUKI TAWAD ...
2000 Volume 53 Issue 10 Pages
1071-1085
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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In an effort to discover a novel cefozopran (CZOP) derivative having excellent antibacterial activity against methicillin-resistant
Staphylococcus aureus (MRSA), we performed chemical modification of the alkoxyimino moiety and imidazo[1, 2-b]pyridazinium group of CZOP. Among the prepared compounds, the cyclopentyloxyimino derivative 7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(
Z)-cyclopentyloxyiminoacetamido]-3-(3, 6-diaminoimidazo[1, 2-b]pyridazinium-l-yl)methyl-3-cephem-4-carboxylate (
20g) showed the most potent anti-MRSA activity, reflecting its high affinity (IC
50=1.6 μg/ml) for penicillin binding protein 2' (PBP2'), although its anti-MRSA activity was slightly inferior to that of vancomycin (VCM). In experimental systemic infection in mice, however,
20g showed activity comparable to that of VCM against MRSA. In addition,
20g showed activity similar or slightly inferior to that of CZOP against
Pseudomonas aeruginosa both
in vitro and
in vivo. Considering its favorable antibacterial activity profile,
20g was considered to be the most promising CZOP derivative for further studies.
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FEDERICO MARIA ARCAMONE, MARIA AURAMURA, ENZO PERROTTA, ATTILIO CREA, ...
2000 Volume 53 Issue 10 Pages
1086-1095
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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The synthesis and biological properties of the new penem antibiotic MEN 10700 (
6) and of its selected oral prodrug MEN 11505 (
8f) are described. MEN 10700 showed a broad spectrum of activity, with high potency both on Gram-positive and Gram-negative strains. It also exhibited good antibacterial activity toward anaerobes and on strains selected for their resistance to other antibacterial agents (cefotaxime- or ceftazidime-resistant Gram-negative strains, ciprofloxacin-resistant
E. coli, extended spectrum β-lactamase producing and cephalosporinase inducible enterobacteria). MEN 10700 showed a very high stability to enzymatic degradation by renal dehydropeptidase DHP-I. After oral administration in rats of the pivaloyloxymethyl ester prodrug MEN 11505, the relative bioavailability of MEN 10700 was calculated as F=43%.
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I. Taxonomy, Production, Isolation and Biological Properties
MASAYUKI IGARASHI, CHIGUSA HAYASHI, YOSHIKO HOMMA, SEIKO HATTORI, NAOK ...
2000 Volume 53 Issue 10 Pages
1096-1101
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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A novel 16-membered lactone antibiotic named tubelactomicin A was isolated from the culture broth of an actinomycete strain. The producing organism, designated MK703-102F1, was identified as a member of
Nocardia. Tubelactomicin A was isolated from the culture broth by Diaion HP20 absorption, ethyl acetate extraction, silica gel and Sephadex LH-20 column chromatographies and centrifugal liquid-liquid partition chromatography (CPC). Tubelactomicin A showed strong activity against acid-fast bacteria including the drug-resistant strains.
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II. Structure Elucidation
MASAYUKI IGARASHI, HIKARU NAKAMURA, HIROSHI NAGANAWA, TOMIO TAKEUCHI
2000 Volume 53 Issue 10 Pages
1102-1107
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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A novel 16-membered lactone antibiotic named tubelactomicin A was isolated from the culture broth of
Nocardia sp. MK703-102F1.
The structure of tubelactomicin A was assigned by spectroscopic analysis and the absolute configuration was determined by X-ray crystallographic analysis.
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TAKAO OHYAMA, YUKO KURIHARA, YASUNORI ONO, TOMIO ISHIKAWA, SHUNICHI MI ...
2000 Volume 53 Issue 10 Pages
1108-1116
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Arborcandins A, B, C, D, E and F, which possess potent 1, 3-β-glucan synthase inhibitory activity, were isolated from the culture broth of a filamentous fungus, strain SANK 17397. Arborcandins are novel cyclic peptides, that are structurally different from known glucan synthase inhibitors such as echinocandins. The l, 3-β-glucan synthases of
Candida albicans and
Aspergillus fumigatus were inhibited by arborcandins with IC
50 ranging from 0.012 to 3 jiLg/ml. The apparent
Ki value of arborcandin C for
C. albicans and
A. fumigatus were 0.12/1M and 0.016 μM, respectively. The inhibition against these two l, 3-β-glucan synthases by arborcandin C was noncompetitive. These compounds exhibited potent fungicidal activity against
Candida spp. with MIC ranging from 0.25 to 8μg/ml. The growth of
A. fumigatus was suppressed by arborcandins with concentrations ranging from 0.063 to 4 μg/ml.
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YASUHIRO IGARASHI, MIO OGAWA, YUKIO SATO, NORIKO SAITO, RYUJI YOSHIDA, ...
2000 Volume 53 Issue 10 Pages
1117-1122
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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A new microbial metabolite, designated fistupyrone, was isolated from the culture broth of a plant-associated
Streptomyces sp. TP-A0569. Fistupyrone inhibited the
in vivo infection of the seedlings of Chinese cabbage by
Alternaria brassicicola TP-F0423, the cause of Alternaria leaf spot, without any
in vitro fungicidal activity.
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FRANK EILBERT, HEIDRUN ANKE, PLOV STERNER
2000 Volume 53 Issue 10 Pages
1123-1129
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Six new dimeric anthraquinone derivatives, neobulgarones A (
3a), B (
3b), C (
4a), D (
4b), E (
5a) and F (
5b), were isolated from the mycelia of the ascomycete
Neobulgaria pura together with the monomeric carviolin (
1) and 1-
O-methylemodin (
2). All new compounds inhibited the formation of appressoria in germinating conidia of
Magnaporthe grisea on inductive (hydrophobic) surface. The compounds exhibited moderate cytotoxic, but no antifungal, antibacterial, or phytotoxic activities.
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Taxonomy, Fermentation, Isolation and Biological Activities
KOICHI NAKAE, YUYA YOSHIMOTO, TSUTOMU SAWA, YOSHIKO HOMMA, MASA HAMADA ...
2000 Volume 53 Issue 10 Pages
1130-1136
Published: October 25, 2000
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A new compound, migrastatin, was isolated from a cultured broth of
Streptomyces sp. MK929-43F1, as an inhibitor of tumor cell migration. It was purified by column chromatographies on silica gel and Sephadex LH-20 and HPLC. Migrastatin has the molecular formula of C
27H
39NO
7 consisting of 14-membered macrolide and glutarimide moiety. It inhibited spontaneous migration of human esophageal cancer EC 17 cells. Migration inhibitory activity of migrastatin was not dependent on cytotoxicity or inhibition of protein synthesis.
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SVEN SILBERBORTH, GERHARD ERKEL, TIMM ANKE, OLOV SIERNER
2000 Volume 53 Issue 10 Pages
1137-1144
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Five novel antibiotics described as irpexans (
1,
2,
3a,
3b,
4) were isolated from fermentations of an
Irpex species in the course of a screening for new inhibitors of AP-1 and NF-κB mediated signal transduction pathways in COS-7 cells using secreted alkaline phosphatase (SEAP) as a reporter gene. The expression of an AP-1 and NF-κB driven SEAP reporter gene was inhibited in a dose dependent manner with 14-acetoxy-15-hydroxyirpexan (
3b) being the most potent compound, followed by 14, 15-irpexanoxide (
2), 14, 15-dihydroxyirpexan (
3a) and 14-acetoxy-22, 23-dihydro-15, 23-dihydroxyirpexan (
4). Irpexan (
1) exhibited no activity. The irpexans (
1,
2,
3a,
3b,
4) are characterized by weak cytotoxic but neither antibacterial nor antifungal activities. All five compounds are terpenoids with a mannose moiety. The structures were elucidated by spectroscopic methods.
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GENHUI CHEN, GUI-YANG-SHENG WANG, XIANG LI, BARBARA WATERS, JULIAN DAV ...
2000 Volume 53 Issue 10 Pages
1145-1153
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Bacterial strains grown in the presence of low concentrations of dimethyl sulfoxide (DMSO) exhibit significant qualitative and quantitative alterations in the production of secondary metabolites. This effect was confirmed for a variety of biosynthetic families, including chloramphenicol (chorismate), thiostrepton (peptide) and tetracenomycin (polyketide), and for natural and recombinant strains of streptomycetes; a similar effect was seen with antibiotic-producing bacilli such as
B. circulans. Increase in antibiotic production was not the result of a change in the growth rate of these organisms, since yields of biomass were similar in media with and without DMSO (up to 3%). We suggest that the addition of compounds such as DMSO provides a means of examining the full biosynthetic potential of microbes and might be used to promote secondary metabolite production. The mode of action of DMSO is not known, but in the cases studied it may act at the level of translation.
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MIDORI HOSHI, TOYOSHIGE ENDO
2000 Volume 53 Issue 10 Pages
1154-1157
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Antibiotic derivative K41-DAI, -DA2 and -DAS (
2-
4), deamicetosyl derivatives of antibiotic K41 (
1), were prepared by acidic degradation of K41 and following hydrogenation reaction. K41-DA2 (
3) showed comparable antimicrobial activities to K41
in vitro but not
in vivo.
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YASUMASA OTA, HIDEYUKI TAMEGAI, FUMITAKA KUDO, HISAKO KURIKI, AYUMI KO ...
2000 Volume 53 Issue 10 Pages
1158-1167
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Butirosin is an interesting 2-deoxystreptamine (DOS)-containing aminoglycoside antibiotic produced by non-actinomycete
Bacilli. Recently we were successful in purification of 2-deoxy-
scyllo-inosose synthase from butirosin-producer
Bacillus circulans as the key enzyme for the biosynthesis of DOS, in cloning of the responsible gene (
btrC), and in its overexpression in
Escherichia coll. The present study involved gene-walking approach, which allowed us to find a gene cluster around
btrC. The function of each gene was further investigated by gene disruption, and the disruptants of
btrB,
btrC,
btrD and
btrM showed no antibiotic producing activity. Therefore, the gene cluster found so far was determined to be a part of the butirosin biosynthetic gene cluster. Functions of some ORFs are also discussed in terms of butirosin biosynthesis on the basis of database search.
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KUNIMOTO HOTTA, ATSUKO SUNADA, YOKO IKEDA, SHINICHI KONDO
2000 Volume 53 Issue 10 Pages
1168-1174
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Fourteen different aminoglycoside antibiotics (AGs) were challenged with aminoglycoside acetyltransferases (AACs) of actinomycete origin in order to examine their 'double stage activity' that is arbitrarily defined as antibiotic activity retainable after enzymatic modification. In kanamycin (KM)-group AGs tested [KM, dibekacin (DKB), amikacin and arbekacin (ABK)], ABK retained activity after acetylations by AAC(3), AAC(2') and AAC(6'). DKB also retained a weak activity after acetylation by AAC(2'). In gentamicin (GM)-group AGs tested [GM, micronomicin, sisomicin (SISO), netilmicin (NTL) and isepamicin], GM, SISO and NTL retained activites after acetylation by AAC(2'). In neomycin (NM)-group AGs tested [ribostamycin, NM, paromomycin], NM retained activity after acetylation by AAC(6') and AAC(2'). None of astromicin (ASTM)-group AGs tested (ASTM and istamycm B) retained activity after acetylation by AAC(2') and AAC(6'). The activities of acetylated ABK derivatives by AAC(3) and AAC(2') were distinctively high> compared to the others.
Streptomyces lividans TK21 containing the cloned
aac genes were markedly sensitive to AGs that retained activities after acetylation, indicating the substantial effect of 'double stage activity'.
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K. UCHIDA, Y. NISHIYAMA, N. YOKOTA, H. YAMAGUCHI
2000 Volume 53 Issue 10 Pages
1175-1181
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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The antifungal activities of FK463 against various pathogenic fungi were tested by standard broth microdilution methods, and compared with the activities of five currently available antifungal agents;
viz., fluconazole (FUCZ), itraconazole, miconazole, amphotericin B and flucytosine. Fourteen clinical isolates of
Candida albicans categorized as FLCZ susceptible, FLCZ susceptible-dose dependent and FLCZ resistant were similarly susceptible to FK463 with geometric (GM) MIC values of 0.010, 0.011 and 0.015 μg/ml, respectively. All of 17 clinical isolates of
Aspergillus fumigatus were inhibited by FK463 at 0.0078μg/ml or lower concentrations. The antifungal activity of FK463 against a wider range of medically important yeasts and filamentous fungi were studied using stock fungal strains. While
Cryptococcus,
Trichosporon,
Fusarium,
Pseudallescheria and
Alternaria species or zygomycetes were scarcely or not inhibited by 16μg/ml of FK463, two
Candida species (
C. albicans,
C. glabrata), as well as all species of
Aspergillus,
Paecilomyces and
Penicillium, were highly susceptible with GM-MICs of ?? 0.008 μg/ml. The other fungal species including several non-
albicans Candida were less susceptible with GM-MICs ranging between 0.016 and μg/ml. MICs of the reference drugs were within the range thus previously reported. These results suggest that FK463 be of use in the treatment of serious fungal infections.
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PETER KNAUTH, HANS REICHENBACH
2000 Volume 53 Issue 10 Pages
1182-1190
Published: October 25, 2000
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The myxobacterial fungicide, ambruticin, kills the yeast,
Hansenula anomala, with high efficacy (MIC 0.05μg/ml), but only when the cells are growing. The earliest effect, observed almost immediately after the addition of the antibiotic, is a transient but substantial increase of intracellular glycerol, followed by an accumulation of triacylglycerols and free fatty acids. At about the time when free fatty acids accumulate, the cells become leaky to low molecular weight compounds. We assume that this leakage kills the cells. The mechanism of action of ambruticin thus appears to be the same as that of the phenylpyrroles,
e.g., pyrrolnitrin,
viz., interference with osmoregulation.
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YOUNG BAE KIM, SE WON KI, MINORU YOSNIDA, SUEHARU HORINOUCHI
2000 Volume 53 Issue 10 Pages
1191-1200
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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Inhibitors of histone deacetylase (HDAC) block cell cycle progression at G1 in many cell types. We investigated the mechanism by which trichostatin A (TSA), a specific inhibitor of HDAC, induces G1 arrest in human cervix carcinoma HeLa cells. TSA treatment induced histone hyperacetylation followed by growth arrest in G1 as well as hypophosphorylation of pRb. The Cdk4 kinase activity was essentially unchanged during the TSA-induced G1 arrest. On the other hand, the arrest was accompanied by down-regulation of kinase activity of Cdk2, although the total protein levels of Cdk2 and its activator Cdc25A were unaffected. Upon TSA treatment, amounts of cyclin E and the CDK inhibitor p21
WAF1/Cip1 were markedly increased, while that of cyclin A was reduced. The induction of p21 and down-regulation of cyclin A correlated well with the decreased Cdk2 activity and cell cycle arrest. Furthermore, gel filtration chromatography showed the association of p21 with the cyclin E-Cdk2 complex, suggesting that the activation of Cdk2 by the enhanced expression of cyclin E is blocked by the increased p21. The elevated expression of p21 is also observed in cells treated with trapoxin and FR901228, structurally unrelated histone deacetylase inhibitors. A human colorectal carcinoma cell line lacking both alleles of the
p21 gene (p21-/-) was resistant to TSA several times more than the parental line (p21+/+). These results suggest that the suppression of Cdk2 kinase activity due to p21 overexpression play a critical role in HDAC inhibitor-induced growth inhibition.
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MUN-CHUAL RHO, MASAHIKO HAYASHI, AKIKO FUKAMI, RIKA OBATA, TOSHIAKI SU ...
2000 Volume 53 Issue 10 Pages
1201-1206
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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7-
O-Benzoylpyripyropene A (7-
O-BzP), a semi-synthetic analog of pyripyropene, was investigated for its reversing effect on multidrug-resistant (MDR) tumor cells. 7-
O-BzP (6.25μg/ml) completely reversed resistance against vincristine and adriamycin in vincristineresistant KB cells (VJ-300) and adriamycin-resistant P388 cells (P388/ADR), respectively. 7-
O-BzP alone had no effect on the growth of drug sensitive and drug-resistant cells. 7-
O-BzP (6.25μg/ml) significantly enhanced accumulation of [
3H]vincristine in VJ-300 cells and completely inhibited the binding of [
3H]azidopine to the P-glycoprotein in VJ-300 cells and P388/ADR cells. The result suggests that 7-
O-BzP effectively reverses P-glycoprotein-related MDR by interacting directly with P-glycoprotein in drug resistant VJ-300 and P388/ADR cells.
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ÁRPÁD KOVÁCS-KULYASSA, PÁL HERCZEGH, FEREN ...
2000 Volume 53 Issue 10 Pages
1207-1211
Published: October 25, 2000
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AKIKO FUKAMI, TOMONORI NAKAMURA, KANAKO KAWAGUCHI, MUN-CHUAL RHO, ATSU ...
2000 Volume 53 Issue 10 Pages
1212-1214
Published: October 25, 2000
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AKIKO FUKAMI, TOMONORI NAKAMURA, YONG-PIL KIM, KAZURO SHIOMI, MASAHIKO ...
2000 Volume 53 Issue 10 Pages
1215-1218
Published: October 25, 2000
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MASAKO OOHORI, KAZUHIKO OTOGURO, TOSHIAKI SUNAZUKA, SUZUKI KUNIHIKO, Y ...
2000 Volume 53 Issue 10 Pages
1219-1222
Published: October 25, 2000
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HIROFUMI YAMAMOTO, KOHJI KAWABATA, SHUICHI TAWARA, HISASHI TAKASUGI, H ...
2000 Volume 53 Issue 10 Pages
1223-1227
Published: October 25, 2000
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KOICHI NAKAE, YUYA YOSHIMOTO, MINORU UEDA, TSUTOMU SAWA, YOSHIKAZU TAK ...
2000 Volume 53 Issue 10 Pages
1228-1230
Published: October 25, 2000
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A Formal Total Synthesis of (+)-Thienamycin
KUNIAKI TATSUTA, MASAAKI TAKAHASHI, NOBORU TANAKA, KEN CHIKAUCHI
2000 Volume 53 Issue 10 Pages
1231-1234
Published: October 25, 2000
Released on J-STAGE: September 19, 2008
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