[Discovery and development of unknown potentialities of microorganisms with special reference to saframycin group antitumor antibiotics].
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.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007546:Isoquinolines / Q000096:biosynthesis / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D012510:Sarcoma 180 / Q000188:drug therapy; D013302:Streptomyces / Q000378:metabolism; D013329:Structure-Activity Relationship; D014410:Tumor Stem Cell Assay
D000903:Antibiotics, Antineoplastic; D007546:Isoquinolines; C034205:saframycin C; C027443:saframycin S; C026925:saframycin A