[Discovery and development of unknown potentialities of microorganisms with special reference to saframycin group antitumor antibiotics]. 1984

T Arai

After a long and energetic world-wide search for antibiotics from actinomycetes, the chances of finding new classes of biologically active compounds from these organisms seem to have drastically diminished. In this paper, sophisticated procedures for finding new potentialities of antibiotic-producing actinomycetes and isolating a novel class of antitumor antibiotics, the saframycins, are described. These antibiotics are satellite antibiotics which are co-produced in minute quantities with streptothricin by a strain of Streptomyces lavendulae. Saframycins, cyano-containing saframycin A in particular, are promising antitumor antibiotics because of their low toxicity to immunologically competent cells and organs, especially the bone marrow. Significant amplification of the yield of saframycin A was attained by the quite unexpected observation that the addition of cyanide to the culture broth significantly increased its production. Subsequent isolation of the saframycin A precursor, decyanosaframycin A or saframycin S, enabled us to prepare two kinds of labeled saframycin A which were critical for the elucidation of the unique molecular action mechanism of the antibiotic. On the basis of studies on saframycin biosynthesis, a method of preparing new saframycin derivatives using resting cells of the producing strain has been developed, and new saframycins with amino functional groups on their N-pyruvoyl side chain were obtained. Their HCl salts are readily soluble in water and are expected to exhibit pharmacodynamic properties different from those of other saframycins.

UI MeSH Term Description Entries
D007546 Isoquinolines A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
D007939 Leukemia L1210 An experimental LYMPHOCYTIC LEUKEMIA of mice. Leukemia L 1210,L 1210, Leukemia,L1210, Leukemia
D002286 Carcinoma, Ehrlich Tumor A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms. Ehrlich Ascites Tumor,Ascites Tumor, Ehrlich,Ehrlich Tumor Carcinoma,Tumor, Ehrlich Ascites
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000903 Antibiotics, Antineoplastic Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. Antineoplastic Antibiotics,Cytotoxic Antibiotics,Antibiotics, Cytotoxic
D012510 Sarcoma 180 An experimental sarcoma of mice. Sarcoma 180, Crocker,Crocker Sarcoma 180
D013302 Streptomyces A genus of bacteria that form a nonfragmented aerial mycelium. Many species have been identified with some being pathogenic. This genus is responsible for producing a majority of the ANTI-BACTERIAL AGENTS of practical value.
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships

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