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GEORGE G. YARBROUGH, DEAN P. TAYLOR, ROBERT T. ROWLANDS, MARK S. CRAWF ...
1993 Volume 46 Issue 4 Pages
535-544
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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TAXONOMY, FERMENTATION, STRUCTURES, AND BIOLOGICAL PROPERTIES
SUI-MING WONG, LASZLO L. MUSZA, GWENDOLYN C. KYDD, RUDY KULLNIG, AMAND ...
1993 Volume 46 Issue 4 Pages
545-553
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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Three new compounds, named fiscalins A, B, and C, were found in culture broth produced by a
Neosartorya fischeri. These compounds inhibit the binding of radiolabeled substance P ligand to the human neurokinin (NK-1) receptor, with
Ki values of 57, 174, and 68 μM, respectively.
Detailed spectroscopic and amino acid analyses led to the elucidation of structures for the three fiscalins. The structures contain an indolyl moiety linked to an athranilic acid derived tricyclic system. The absolute configuration of fiscalin A was determined by X-ray crystallography and chiral amino acid analysis. The presence of fiscalins was detected directly in crude cellular extracts using LC-MS methods.
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MIN CHU, IMBI TRUUMEES, IJI GUNNARSSON, W. ROBERT BISHOP, WILLIAM KREU ...
1993 Volume 46 Issue 4 Pages
554-563
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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Four novel platelet activating factor (PAF) antagonists, Sch 47918, Sch 49026, Sch 49027 and Sch 49028, were isolated from the fermentation broth of the fungal culture,
Phoma sp. (ATCC 74077). The structures of these compounds were elucidated by spectroscopic methods. The structure and stereochemistry of the first isolated component, Sch 47918, were confirmed by single crystal X-ray diffraction analysis. Sch 49028, the most active component, was found to inhibit PAF-induced human platelet aggregation
in vitro with an IC
50 of 1.26 μM. However, this compound was inactive
in vivo at 5 mg/kg, iv against PAF-induced bronchospasm in guinea pigs.
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HIROSHI NISHIOKA, TSUTOMU SAWA, YOSHIKAZU TAKAHASHI, HIROSHI NAGANAWA, ...
1993 Volume 46 Issue 4 Pages
564-568
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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In the course of a screening program for inhibitors of epidermal growth factor (EGF)-induced phosphatidylinositol turnover in human epidermoid carcinoma cell line A431, we discovered two novel compounds of the piericidin family from the culture broth and mycelia of a
Streptomyces strain MJ288-OF3. We named them piericidin B
5 and B
5 N-oxide. By NMR and mass spectrometric analyses, the molecular formulas of piericidin B
5 and B
5 N-oxide were determined to be C
27H
41N0
4 (MW 443) and C
27H
41NO
5 (MW 459), respectively. Piericidin B
5 and B
5 N-oxide inhibited phosphatidylinositol turnover of A431 cells with IC
50s of 10.0 μg/ml and 1.1 μg/ml, respectively.
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YUKIMASA NOZAKI, TSUNEAKI HIDA, SFFIGEMI IINUMA, TAKAFUMI ISHII, KATSU ...
1993 Volume 46 Issue 4 Pages
569-579
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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A potent angiogenesis-inhibitory compound TAN-1120 was found to be produced by a
Streptomyces species isolated from a soil sample. The producing organism was characterized as a new subspecies of
S. triangulatus and named
S. triangulatus subsp.
angiostaticus subsp. nov. due to its specific ability to produce the compound. This substance was isolated as a red powder by a combination of organic solvent extraction, silica gel column chromatography and preparative HPLC using an ODS column. Its structure was elucidated by chemical reactions and spectral analyses to be a new baumycin-group anthracycline. Reduction of TAN-1120 gave two compounds, a deoxy derivative and baumycin A1. TAN-1120 showed remarkably potent angiostatic activity in two conventional angiogenesis assay systems
in vivo, while doxorubicin and daunomycin had far weaker activity. It strongly inhibited proliferation of vascular endothelial cells but did not prevent capillary cord formation
in vitro by the endothelial cells on extracellular matrix-coated plates. TAN-1120 is one of the most potent angiostatic agents reported.
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I. TAXONOMY, FERMENTATION AND BIOLOGICAL ACTIVITIES
KYOICHIRO SAITOH, OSAMU TENMYO, SATOSHI YAMAMOTO, TAMOTSU FURUMAI, TOS ...
1993 Volume 46 Issue 4 Pages
580-588
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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A directed search for antibiotics active in a syncytium formation inhibition assay using a co-culture of HeLa-T4 cells expressing CD4 antigen and BSC-1 cells expressing gp-120 led to the isolation of pradimicin S, a new member of the pradimicin family. The producing strain (AA0851) was characterized as a new species of
Actinomadura for which the name
Actinomadura spinosa sp. nov. is proposed. Production of pradimicin S by strain AA0851 was significantly improved by addition of ferrous sulfate (0.1-0.4%) to the production medium. Pradimicin S showed potent activity against human immunodeficiency virus (HIV) LAV
BRU strain in a CPE assay, and moderate activity against influenza virus type A. The antibiotic was active against a wide variety of fungi and yeasts
in vitro and demonstrated
in vivo efficacy against a systemic
Candida albicans infection in mice.
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I. TAXONOMY, PRODUCTION, ISOLATION, PHYSICO-CHEMICAL AND BIOLOGICAL PROPERTIES
TAMOTSU FURUMAI, TOSHIFUMI HASEGAWA, MASATOSHI KAKUSHIMA, KIYOSHI SUZU ...
1993 Volume 46 Issue 4 Pages
589-597
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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Pradimicins T1 and T2, new members of the pradimicin family of antibiotics, were produced by an actinomycete strain AA3798. Pradimicin Tl exhibited potent activity against a wide spectrum of fungi
in vitro and demonstrated efficacy against systemic
Candida albicans and
Aspergillus fumigatus infections in mice.
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II. STRUCTURES AND BIOSYNTHESIS
TOSHIFUMI HASEGAWA, MASATOSHI KAKUSHIMA, MASAMI HATORI, SHIMPEI ABURAK ...
1993 Volume 46 Issue 4 Pages
598-605
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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Pradimicins T1 and T2 are new members of the pradimicin family of antibiotics produced by an actinomycete strain AA3798. Pradimicins T1 and T2 are dihydrobenzo[
a]naphthacenequinones substituted with 3 and 2 sugar moieties, respectively. The salient feature in their structures is an L-xylose attached to the phenolic hydroxyl group at C-11. Bioconversion experiments using a blocked mutant B-54 of strain AA3798 not only explored a plausible biosynthetic pathway of pradimicins T1 and T2, but also provided evidence of 5
S, 6
S configuration.
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TAXONOMY, FERMENTATION AND BIOLOGICAL ACTIVITY
NOZOMI KATAYAMA, SHOJI FUKUSUMI, YASUNORI FUNABASHI, TOMOYUKI IWAHI, H ...
1993 Volume 46 Issue 4 Pages
606-613
Published: April 25, 1993
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Two Gram-negative bacteria were found to produce the new antibacterial antibiotics TAN-1057 A, B, C arid D. The producing bacteria were characterized and designated as
Flexibacter sp. PK-74 and PK-176. These antibiotics were active against Gram-negative and Gram-positive bacteria, including methicillin-resistant
Staphylococcus aureus. TAN-1057 A inhibited protein biosynthesis in
Escherichia coli and
S. aureus. It showed excellent protective effects against an experimental methicillin-resistant
S. aureus infection in mice.
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Z. H. AHMED, R. R. FIALA, M. W. BULLOCK
1993 Volume 46 Issue 4 Pages
614-622
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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A total of 76 mCi of
14C LL-F28249-α, nemadectin (
1), having a specific activity of 35.2μCi/mg was isolated from a fermentation using a mixture of approximately 600 mCi of
14C carboxyl labeled acetate, propionate and isobutyrate. Nemadectin was used to synthesize carbon-14 labeled moxidectin which is being developed as a highly efficient ectoparasitic anthelminth. The labeled positions were determined by
13C NMR analysis of
13C nemadectin which was obtained by similar incorporation of
13C carboxyl labeled acetate, propionate and isobutyrate.
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Y. K. TONY LAM, PING DAI, DEBORAH L. ZINK, ALISON J. SMITH, NAILIN W. ...
1993 Volume 46 Issue 4 Pages
623-630
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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Fifteen 13-ester, 13-carbanilate and 15-hydroxy derivatives of virginiamycin M
1 were synthesized and evaluated for their abilities to inhibit a) binding to the cholecystokinin receptor subtypes in guinea-pig brain (CCK-B) and rat pancreas (CCK-A), and b) microbial growth.
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MODIFICATIONS OF THE SUGAR PART
SHIMPEI ABURAKI, HARUHIRO YAMASHITA, TAKESHI OHNUMA, HAJIME KAMACHI, T ...
1993 Volume 46 Issue 4 Pages
631-640
Published: April 25, 1993
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Modifications at the sugar part of pradimicins were carried out by glycosidations of the aglycones or chemical transformations of natural pradimicins and their antifungal activity was evaluated. Among them, some of the D-xylose-modified derivatives (
14,
17,
24) showed activity comparable to that of pradimicin A. The structure-activity relationships obtained through there sutdies clarified the role of the sugar part in the manifestation of antifungal activity: The 5-
O-(6-deoxy-β-D-sugar) is essential for activity and 2'-
epi, 3'-oxo and 4'-deoxy sugar derivatives retain activity against yeasts.
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S. ADAM, R. THEN, P. ANGEHRN
1993 Volume 46 Issue 4 Pages
641-646
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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A series of (6
R)-6-(substituted methyl)penicillanic acid sulfones has been prepared starting from the corresponding 6-(substituted methylene)penicillanates. The new sulfones
9a,
9b,
9c and
9d have been shown to be potent β-lactamase inhibitors.
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SELECTIVE METHYLATION AT THE C-6 HYDROXYL GROUP OF ERYTHROMYCIN A OXIME DERIVATIVES AND PREPARATION OF CLARITHROMYCIN
YOSHIAKI WATANABE, SHIGEO MORIMOTO, TAKASHI ADACHI, MASATO KASHIMURA, ...
1993 Volume 46 Issue 4 Pages
647-660
Published: April 25, 1993
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Although erythromycin A contains five hydroxyl groups, regioselective methylation at the C-6 hydroxyl group was achieved to the extent of 90% when a 9-
O-substituted erythromycin A 9-oxime was employed as substrate.
The methylation and its selectivity are dependent on an
O-protecting group at the 9-oxime, solvent, base, and methylating reagent. In particular, the use of a polar aprotic solvent is indispensable for the methylation. Among the 9-oxime derivatives, 2'-
O, 3'-
N-bis(benzyloxycarbonyl)-
N-demethylerythromycin A 9-[
O-(2-chlorobenzyl)bxime] was the most important intermediate for the synthesis of clarithromycin (6-
O-methylerythromycin A).
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ADRIANO MALABARBA, ROMEO CIABATTI, ROBERTO SCOTTI, BETH P. GOLDSTEIN
1993 Volume 46 Issue 4 Pages
661-667
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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A series of octapeptide derivatives of teicoplanin-A2 component 2 (CTA/2), its aglycone (TD), and the L-lysyl derivatives of an amide of CTA/2 and TD, were prepared by condensation of the terminal amino group with
N-hydroxysuccinimidyl esters of
tert-butyloxycarbonyl (BOC) L-- and D-amino acids, followed by acidic (TFA) removal of the BOC protecting function.
The antimicrobial properties of these compounds were compared with those of the corresponding unmodified antibiotics and their
N15-acetyl derivatives. The most active derivatives were the octapeptides with
N-terminal glycine or lysine whose
in vitro activity was comparable to that of the parent teicoplanins. The glycinyl and lysyl derivatives of CTA/2 showed better activity than CTA/2 against clinical isolates of
Staphylococcus epidermidis and
S. haemolyticus for which teicoplanin MICs were relatively high. No significant difference in their antibacterial activity was observed between octapeptides containing L- or D-lysine.
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ADRIANO MALABARBA, ROMEO CIABATTI, JÜRGEN KETTENRING, ROBERTO SCO ...
1993 Volume 46 Issue 4 Pages
668-675
Published: April 25, 1993
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The synthesis and biological properties of a series of
N63-carboxamides of 15-
N-alkylated derivatives of teicoplanin A2 (CTA) and its aglycone (TD) are described. Among the compounds, those carrying hydrophilic groups or ionizable amino functions on the
N15-alkyl chain are more soluble in water than parent
N15-methylated or unmodified amides.
Selected compounds were more active
in vitro than CTA or TD, and a few of them were also slightly more efficacious
in vivo than the parent antibiotics in streptococcal septicemia in the mouse. Their degree of activity varied with the structure and length of the
N15-alkyl chains.
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NOBUO HOSOKAWA, HLRONOBU ILNUMA, HIROSHI NAGANAWA, MASA HAMADA, TOMIO ...
1993 Volume 46 Issue 4 Pages
676-678
Published: April 25, 1993
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NOBUAKI NARUSE, HARUAKI YAMAMOTO, SHINJI MURATA, YOSUKE SAWADA, YASUO ...
1993 Volume 46 Issue 4 Pages
679-681
Published: April 25, 1993
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KUMIKO W. SHIMOTOHNO, TOYOSHIGE ENDO, KAZUO FURIHATA
1993 Volume 46 Issue 4 Pages
682-684
Published: April 25, 1993
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NOBUAKI NARUSE, SATOSHI YAMAMOTO, HARUAKI YAMAMOTO, SHOICHIRO KONDO, S ...
1993 Volume 46 Issue 4 Pages
685-686
Published: April 25, 1993
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MLTSUAKI TSUNAKAWA, NORIYUKI OHKUSA, SEIKICHI KOBARU, YUKIO NARITA, SH ...
1993 Volume 46 Issue 4 Pages
687-688
Published: April 25, 1993
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KEIJI HASUMI, KIYOSHI TACHIKAWA, KAORU SAKAI, SHIGEO MURAKAWA, NOBUJI ...
1993 Volume 46 Issue 4 Pages
689-691
Published: April 25, 1993
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NAOKI ABE, NOBUYASU ENOKI, YASUKAZU NAKAKITA, HIDEAKI UCHIDA, TAKEHIKO ...
1993 Volume 46 Issue 4 Pages
692-697
Published: April 25, 1993
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RAMIN FAGHIN, TOM PAGANO, JIM MCALPINE, KEN TANAKA, JAKE PLATTNER, PAU ...
1993 Volume 46 Issue 4 Pages
698-700
Published: April 25, 1993
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IKUMI URUSHIBATA, AKIRA ISOGAI, SHOGO MATSUMOTO, AKINORI SUZUKE
1993 Volume 46 Issue 4 Pages
701-703
Published: April 25, 1993
Released on J-STAGE: April 19, 2006
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