Bisucaberin, a new siderophore, sensitizing tumor cells to macrophage-mediated cytolysis. II. Physico-chemical properties and structure determination

The structure of bisucaberin, a new siderophore, was determined to be 1,12-dihydroxy-1,6,12,17-tetraazacyclodocosane-2,5,13,16-tetron e by spectroscopic analysis and X-ray crystallographic analysis. The molecule of bisucaberin consists of a cyclic dimer of 1-hydroxy-1,6-diazaundecane-2,5-dione moiety and is closely related to nocardamine, the trimer of the same moiety.     

Swalpamycin, a new macrolide antibiotic. I. Taxonomy of the producing organism, fermentation, isolation and biological activity

A new macrolide antibiotic, swalpamycin, has been isolated from the culture broth of Streptomyces sp. Y-84,30967. Taxonomically the producing organism most closely resembles Streptomyces anandii and has therefore been named S. anandii subsp. swalpus. Swalpamycin is a neutral 16-membered macrolide active against Gram-positive bacteria including erythromycin-resistant strains.     

PS-5, a new beta-lactam antibiotic. I. Taxonomy of the producing organism, isolation and physico-chemical properties.

Antibiotic PS-5 is a new beta-lactam antibiotic isolated from fermentation broths of Streptomyces sp. strain A271. The strain was considered to be a new subspecies of Streptomyces cremeus and the name, Streptomyces cremeus subsp. auratilis, was proposed. Fermentative production, isolation and physico-chemical properties of PS-5 are described.     

Deacetylravidomycin N-oxide, a new antibiotic. Taxonomy and fermentation of the producing organism and isolation, structure and biological properties of the antibiotic

Streptomyces ravidus S50905 was found to produce a new antibiotic, deacetylravidomycin N-oxide, together with ravidomycin and deacetylravidomycin in a culture medium containing sodium anthraquinone-beta-sulfonate. The structure of this new compound was determined from NMR and mass spectrometric data, and further confirmed by chemical synthesis from deacetylravidomycin. Deacetylravidomycin N-oxide was antitumor active against P388 leukemia and Meth A fibrosarcoma in a wide range of doses, and considerably less toxic than deacetylravidomycin. Its antibacterial activity was less potent than deacetylravidomycin. Ravidomycin N-oxide was also synthesized from ravidomycin and its biological properties were tested.     

Novel antifungal antibiotics maniwamycins A and B. I. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological properties

Two antifungal antibiotics maniwamycins A and B were isolated from the culture broth of a strain of actinomycetes, which were classified as Streptomyces prasinopilosus. These antibiotics were isolated by resin absorption and extraction with EtOAc and purified by column chromatography. Both antibiotics were found to be new azoxy substances from their physico-chemical properties. They showed broad antifungal spectra.     

Kedarcidin, a new chromoprotein antitumor antibiotic. I. Taxonomy of producing organism, fermentation and biological activity

Strain L585-6 (ATCC 53650) is an actinomycete isolated from a soil sample collected in Maharastra State, India. It produces a new chromoprotein antitumor antibiotic, designated kedarcidin. Taxonomic studies demonstrated that strain L585-6 is an unidentified and unknown actinomycete. Kedarcidin shows potent antitumor activity against implanted P388 leukemia (3.3 micrograms/ml/kg) and B16 melanoma (2 micrograms/kg) in mice. Kedarcidin also shows potent antimicrobial activity against Gram-positive bacteria but no activity against Gram-negative bacteria.     

Neihumicin, a new cytotoxic antibiotic from Micromonospora neihuensis. I. The producing organism, fermentation, isolation and biological properties

A new cytotoxic and antifungal antibiotic, neihumicin, was isolated from the culture broth of a soil isolate identified as Micromonospora neihuensis Wu, sp. nov. Neihumicin shows in vitro cytotoxicity against KB tissue culture cells (ED50 0.94 micrograms/ml) as well as antifungal activity against Saccharomyces cerevisiae ATCC 9763.     

New antibiotic, isohematinic acid. I. Taxonomy of producing organism, fermentation and isolation

New antibiotic, isohematinic acid, was found in the culture broth of an actinomycete strain SANK 61681, which was identified as a strain of Actinoplanes philippinesis. Fermentation of isohematinic acid was performed by conventional submerged culture in a 600-liter fermentor. Isolation of isohematinic acid was performed by adsorption of the antibiotic from the culture filtrate on a column of Diaion HP-20 followed by elution with aqueous acetone and extraction with ethyl acetate. Isohematinic acid was finally crystallized from hot methanol.     

Thrazarine, a new antitumor antibiotic. I. Taxonomy, fermentation, isolation and biological properties

Thrazarine, O-[(3R)-2-diazo-3-hydroxybutyryl)]-L-serine, is a new antitumor antibiotic produced by Streptomyces coerulescens MH802-fF5. Thrazarine was isolated from culture filtrate by Sephadex LH-20 column chromatography and reversed phase HPLC. Thrazarine induced cytolysis of tumor cell lines co-cultured with nonactivated macrophages. This effect was tumor specific because the nontumorigenic cells were not lysed by macrophages in the presence of thrazarine. Thrazarine inhibited DNA synthesis and growth of tumor cells directly. It showed neither antimicrobial activity nor the inhibition of transamidation reactions in contrast to azaserine. Toxicities of thrazarine were much weaker than those of azaserine.     

Pholipomycin, a new member of phosphoglycolipid antibiotics. I. Taxonomy of producing organism and fermentation and isolation of pholipomycin

Pholipomycin is a new member of the phosphoglycolipid family of antibiotics. Taxonomic studies of the producing organism revealed that it has morphologically characteristic aerial mycelia in which two to three spores are borne usually on short and clavate side branches. The species name, Streptomyces lividoclavatus, has been proposed. Pholipomycin is produced mainly in the solid residue of the fermentation culture broth and is isolated by methanol extraction of the mycelial cake followed by purification on ion-exchange resin and silica gel chromatography.     

Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus. I. Taxonomy of producing organism, fermentation and biological activity

Strain C39108-P210-51 (ATCC 53653), an actinomycete isolated from a soil sample collected in India, was found to produce a new antitumor antibiotic, designated himastatin. Taxonomic studies on its morphological, cultural and physiological characteristics identified this producing strain as Streptomyces hygroscopicus C39108-P210-51. Himastatin shows antimicrobial activity against Gram-positive bacteria but it is inactive against Gram-negative bacteria. Himastatin prolongs the life span of mice inoculated with P388 leukemia and B16 melanoma cells.     

Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. I. Taxonomy of the producing strain, fermentation, isolation and biological properties

A new diterpene antitumor antibiotic, myrocin C, has been isolated from the culture filtrate of a soil fungus, Myrothecium verrucaria strain No. 55. The antibiotic was effective against Gram-positive bacteria, fungi and yeasts, and prolonged the life span of mice bearing Ehrlich ascites carcinoma.     

7-Hydroxyguanine, a novel antimetabolite from a strain of Streptomyces purpurascens. I. Taxonomy of producing organism, fermentation, isolation and biological activity

Strain A-347, an actinomycete isolated from a soil sample, was found to produce a new antimetabolite, 7-hydroxyguanine. The aerial mycelium formed spiral spore chains with spiny spore surface. The chemical composition of strain A-347 indicated that it was an actinomycete of cell wall Type I. From its morphological, cultural, physiological characteristics and direct comparison with the type culture, this strain was classified as Streptomyces purpurascens. 7-Hydroxyguanine was purified from the broth filtrate by ion exchange chromatography and crystallized from hot 2 M NH4OH. 7-Hydroxyguanine inhibited the growth of experimental tumors such as L1210 leukemia.     

F13459, a new derivative of mycophenolic acid. I. Taxonomy, isolation, and biological properties

In the course of screening for inhibitors of intracellular trafficking of glycoprotein, a new inhibitor, F13459 was isolated from the culture broth of a Penicillium sp. It was purified using solvent extraction, silica gel, Sephadex LH-20 and ODS column chromatography. From structural analysis, F13459 was a derivative of mycophenolic acid, an inhibitor of inosine 5'-monophosphate dehydrogenase. F13459 inhibited hemagglutinin synthesis of NDV at concentrations more than 25 microg/ml. However, syncytium formation as a result of cell surface expression of F-glycoprotein of NDV was inhibited at concentrations of F13459 lower than those required for appreciable inhibition of glycoprotein synthesis.     

Aculeximycin, a new antibiotic from Streptosporangium albidum. I. Taxonomy of producing organism and fermentation

A soil isolate of actinomycete, strain TI-1, was found to produce a new antibiotic aculeximycin which killed insects as well as inhibited the growth of bacteria, yeasts and molds in vitro. Yellowish gray colonies on agar media, formation of spherical to oval sporangia at the tip of aerial mycelium and the presence of meso-diaminopimelic acid and madurose in the cell wall ascribed this strain to genus Streptosporangium. From its morphological, cultural and physiological characteristics, the strain was determined to be S. albidum. Production of aculeximycin was carried out by conventional submerged culture: the highest antibiotic titer obtained was 1,250 micrograms/ml.     

A novel macromolecular antibiotic, SN-07. Taxonomy of producing organism, isolation, characterization and biological activities

A novel macromolecular antibiotic SN-07 was obtained from the cultural supernatant of Actinomadura roseoviolacea var. miuraensis nov. var. The antibiotic was soluble in water, had a molecular weight of 18,000-22,000 daltons in 50 mM Tris-HCl buffer, pH 7.0, containing 2.0 M KCl as compared with authentic proteins. Its major constituents were nucleic acids. The substance had antibacterial activity against Gram-positive bacteria. It was also effective against lymphocytic leukemia P388 in vivo.     

A new 5'-nucleotidase inhibitor, nucleoticidin. I. Taxonomy, fermentation, isolation and biological properties

A new 5'-nucleotidase inhibitor named nucleoticidin was produced by Pseudomonas sp. YM-3229G. It was isolated from a fermentation broth by trichloroacetic acid extraction, ethanol precipitation and Dowex 1 and DEAE-52 column chromatography. It inhibited 5'-nucleotidase activity of snake venom and rat liver membrane. It also showed antitumor activity against solid type Sarcoma 180.     

BE-31405, a new antifungal antibiotic produced by Penicillium minioluteum. I. Description of producing organism, fermentation, isolation, physico-chemical and biological properties

A new antifungal antibiotic, BE-31405, was isolated from the culture broth of a fungal strain, Penicillium minioluteum F31405. BE-31405 was isolated by adsorption on high porous polymer resin (Diaion HP-20), followed by solvent extraction, precipitation and crystallization. BE-31405 showed potent growth inhibitory activity against pathogenic fungal strains such as Candida albicans, Candida glabrata and Cryptococcus neoformans, but did not show cytotoxic activity against mammalian cells such as P388 mouse leukemia. The mechanism studies indicated that BE-31405 inhibited the protein synthesis of C. albicans but not of mammalian cells.