Studies of platelet activating factor (PAF) antagonists from microbial products. II. Pharmacological studies of FR-49175 in animal models.
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Anaphylaxis↗
Biomedical subjects
M Kohsaka
Publications and source records attributed to M Kohsaka.
A new antitumor antibiotic, chromoxymycin. II. Production, isolation, characterization and antitumor activity.
Chromoxymycin is a new antitumor antibiotic produced by a new actinomycete named Streptomyces libani subsp. rubropurpureus No. 6362. Chromoxymycin is active against P388 leukemia and B16 melanoma in mice, and has weak antibacterial activity against some Gram-positive bacteria.
Animals↗
FR-900452, a specific antagonist of platelet activating factor (PAF) produced by Streptomyces phaeofaciens. I. Taxonomy, fermentation, isolation, and physico-chemical and biological characteristics.
A PAF antagonist, designated as FR-900452, was isolated from fermentation products of Streptomyces phaeofaciens and the molecular formula was determined as C22H25N3O3S. The compound inhibited PAF-induced rabbit platelet aggregation with an IC50 of 3.7 X 10(-7)M, but was much less active against collagen-, arachidonic acid- or ADP-induced aggregation (IC50; 6.4 X 10(-5), greater than 10(-4) or greater than 10(-4)M, respectively).
Adenosine Diphosphate↗
A new antitumor antibiotic, chromoxymycin. I. Taxonomic studies on the producing strain: a new subspecies of the genus Streptomyces.
A new subspecies of the genus Streptomyces, for which the name S. libani subsp. rubropurpureus subsp. nov. is proposed, is described. Soil isolate, strain No. 6362, produces a new antitumor substance chromoxymycin. The strain has a gray or red spore mass color, spiral spore chains with smooth spores, is nonchromogenic, and utilizes most carbon sources. Strain No. 6362 is most closely related to S. libani, although there are differences in colorization of reverse colony and spore chain morphology between each other. Those differences are not enough to establish a new species. It is suitable to consider that strain No. 6362 is identified as a new subspecies in the species of S. libani.
Antibiotics, Antineoplastic↗
A new antitumor complex, WF-1360, WF-1360A, B, C, D, E and F.
A complex of the new antitumor antibiotics (WF-1360, WF-1360A, B, C, D, E and F) was produced by Rhizopus sp. No. F-1360. Structural studies of these compounds suggested that they were novel 16-membered-ring lactones having an oxazole ring in their structures. WF-1360 was found to be identical with rhizoxin (1) and WF-1360B, C, E and F were determined to be homologues of 1 with structures 2, 3, 4 and 5, respectively. These compounds were cytotoxic when tested on P388 leukemia cells in vitro. WF-1360 was highly active against leukemia L1210 and melanoma B16. They also exhibited potent antifungal activities, but weak antimicrobial activities against some Gram-positive or negative bacteria.
Animals↗
Structure and synthesis of WB-3559 A, B, C and D, new fibrinolytic agents isolated from Flavobacterium sp.
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Chemical Phenomena↗
Structure activity relationships of synthetic antibiotic analogues of chryscandin.
Anti-yeast activity with a series of chryscandin derivatives showed that the O-methyl-L-tyrosyl moiety is not always required for activity at the target site. On the other hand, the adenyl-3'-aminoribofuranuronic acid moiety seems to be essential for biological activity. Therefore, the various acyl derivatives on the amino group of the sugar part of the nucleoside were synthesized. 1-(6-Amino-9H-purin-9-yl)-3-(S-benzyl-L-cysteinylamino)- 1,3-dideoxy-beta-D-ribofuranuronic acid (16) showed the highest efficacy among them against Candida albicans. It exhibited sixteen-fold enhanced activity in vitro compared with that of native chryscandin. The in vivo activity of 16 against experimental infection of C. albicans showed the almost same as that of 5-fluorocytosine and a superior to that of ketoconazole.
Animals↗
Biphenomycins A and B, novel peptide antibiotics. I. Taxonomy, fermentation, isolation and characterization.
Biphenomycin A, C23H28N4O8, and biphenomycin B, C23H28N4O7, were isolated from the cultured broth of Streptomyces griseorubiginosus No. 43708. The antibiotics are active in vitro and in vivo against bacteria, and are especially potent against Gram-positive bacteria. The acute toxicity of biphenomycin A is very low in mice.
Animals↗
Studies on WB-3559 A, B, C and D, new potent fibrinolytic agents. I. Discovery, identification, isolation and characterization.
WB-3559 A, B, C and D were produced by a bacterium which was classified as a member of the genus Flavobacterium. These compounds were purified by solvent extraction followed by chromatography on silica gel and then isolated by HPLC. The chemical structures were determined on the basis of chemical and spectroscopic evidence as in the succeeding papers. WB-3559 A, B, C and D stimulated rabbit plasma euglobulin clot lysis time. A chemically synthesized compound (WB-3559 D-syn) stimulated mouse plasma euglobulin clot lysis time when injected intravenously.
Animals↗
Studies on WB-3559 A, B, C and D, new potent fibrinolytic agents. II. Structure elucidation and synthesis.
The structures of WB-3559 A, B, C and D, new fibrinolytic agents isolated from Flavobacterium sp. No. 3559, have been elucidated to be as shown in 1, 2, 3 and 4, respectively, on the basis of chemical and spectroscopic evidence. Total synthesis of WB-3559 D (4) was achieved starting from the optically active aldehyde 14.
Chemical Phenomena↗
Chaetiacandin, a novel papulacandin. I. Fermentation, isolation and characterization.
Chaetiacandin, a new anti-yeast antibiotic structurally related to papulacandin, was isolated from a culture of Monochaetia dimorphospora. The fermentation, isolation, and physico-chemical and biological properties are reported. The molecular formula of this compound was determined as C43H60O16.
Aminoglycosides↗
Lavendomycin, a new antibiotic. I. Taxonomy, isolation and characterization.
Lavendomycin, a new basic peptide antibiotic containing novel amino acids, has been isolated from the culture broth of a streptomyces designated as Streptomyces lavendulae subsp. brasilicus. The antibiotic obtained as colorless crystals (C29H50N10O8, MW 666) is active against Gram-positive bacteria in vitro and in vivo, however, inactive against Gram-negative bacteria and fungi. An acute toxicity of the antibiotic in mice was LD50 greater than 2 g/kg by subcutaneous injection.
Animals↗
New antitumor antibiotics, FR-900405 and FR-900406. I. Taxonomy of the producing strain.
An actinomycete which was isolated from a soil sample produces new antitumor substances. The morphological and cultural characteristics of the strain resemble those of the genera Streptomyces Waksman and Henrici 1943 and Actinomadura Lechevalier and Lechevalier 1970. Cell wall composition analysis showed that strain No. 6049 contained meso-2,6-diaminopimelic acid in its cell wall, and madurose in whole-cell sugars. No sporangia, zoospores or fragmentations of vegetative mycelium are observed. From these results, strain No. 6049 is designated as Actinomadura pulveracea sp. nov.
Actinomycetales↗
New antitumor antibiotics, FR-900405 and FR-900406. II. Production, isolation, characterization and antitumor activity.
The new antitumor antibiotics, FR-900405 and FR-900406, were isolated from the culture broth of Actinomadura pulveracea sp. nov. No. 6049. These compounds which contain sulfur in the molecule, represent a novel class of antitumor agents. FR-900405 and FR-900406 are highly active in mice against experimental tumors and exhibit antimicrobial activity against Gram-positive and Gram-negative bacteria and fungi.
Actinomycetales↗
Studies of an immunomodulator, swainsonine. I. Enhancement of immune response by swainsonine in vitro.
Swainsonine isolated from Metarhizium sp., was found to enhance the activities of the mouse immune system in vitro. Concanavalin A stimulated lymphocyte proliferation and proliferative response in mixed lymphocytes culture, which were suppressed by immunosuppressive factor obtained from serum of sarcoma 180 tumor bearing mouse, were restored to normal levels by the addition of swainsonine. Furthermore, the concanavalin A induced incorporation of [3H]thymidine into mouse spleen cells was remarkably increased by treatment with swainsonine over a wide dose range, From studies using fluorescence activated cell sorting, swainsonine was shown to enhance the expression of concanavalin A receptors of spleen cells.
Adjuvants, Immunologic↗
Studies of an immunomodulator, swainsonine. II. Effect of swainsonine on mouse immunodeficient system and experimental murine tumor.
We examined the effect of swainsonine on antibody response to sheep red blood cells (SRBC) in immunodeficient mice which were treated with immunosuppressive factor or antitumor drugs, or inoculated with sarcoma 180 ascites tumor. The administration of swainsonine restored the capacities of the immunodeficient mice to produce antibody against SRBC. Furthermore, swainsonine inhibited completely the growth of sarcoma 180 ascites tumor in mice. Swainsonine also reduced lung metastases of B16 melanoma in mice. These results suggest that swainsonine has potential as an immunomodulator for the treatment of immunocompromised hosts.
Adjuvants, Immunologic↗
New antitumor antibiotic, FR-900405. III. Mechanism of action of FR-900405.
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Animals↗
Inhibitory effects of various 3'-deoxyribonucleotides on DNA polymerase alpha 2-primase from developing cherry salmon (Oncorhynchus masou) testes.
DNA polymerase alpha 2-primase has been purified 2750 fold from developing cherry salmon (Oncorhynchus masou) testes by the following purification steps: fractional extraction, phosphocellulose (1st), ammonium sulfate fractionation, DEAE-cellulose, phosphocellulose (2nd), hydroxylapatite and single-stranded DNA-cellulose column chromatographies. Final preparation of this enzyme has a specific activity of 107,000 units/mg protein (activated salmon sperm DNA as template-primer). DNA primase activity (rGTP dependent incorporation of labelled dGMP into poly (dC) or rNTP dependent incorporation of dNMP into M13 single-stranded DNA) was tightly associated with DNA polymerase alpha activity during all stage of this purification process. Inhibition of DNA primase activity by six kinds of 3'-deoxyribonucleotides was studied by using rNTP dependent DNA synthesis on M13 DNA as template. The inhibition constants (Ki) were larger than those of DNA-dependent RNA polymerases I and II. However, Ki/Km values were very close.
Animals↗