A new antitumor antibiotic is produced in fermentation liquors of Streptomyces zelensis sp.n. The antibiotic is biologically active at extremely low concentrations. At 40 pg/ml, it inhibited 90% of the growth of L1210 cells in culture in tube dilution assays. The minimal inhibitory concentrations against Gram-positive bacteria is between 1-10 ng/ml, while these values for Gram-negative bacteria and fungi are mostly under 1 jig/ml. A microbiological assay with Bacillus subtilis can detect concentrations of I-2 ng/ml. A new antitumor antibiotic, CC-1065, was discovered in our laboratories''. It was isolated from fermentation liquors of a new species of Streptomyces which was designated Streptomyces zelensis DIETZ and Li sp. n. (UCH-5923). This communication describes the production of the drug, the taxonomic study of the producing microorganism, the in vitro activity, and the microbiological assay. The methods of isolation and evaluation against experimental animal tumors will be described in separate communications.
CC-1065 (NSC 298223) is a potent new antitumor antibiotic with a unique structure produced by Streptomyces zelensis. Improved production, isolation, and assay methods are described along with physico-chemical properties and antitumor activity. Screening for soil cultures producing agents displaying both cytotoxic activity against L1210 cells in culture and in vivo activity against P388 leukemia in mice afforded a culture, Streptomyces zelensis, producing a new, potent antitumor antibiotic, CC-1065. Its production, in vitro biological activity, microbiological assays, and taxonomy have already been described1) ; a preliminary communication announced the structure2) shown in Fig. 1. Details of the structure determination have recently been described3). A molecular model of CC-1065 displayed a remarkable curvature, shape,
A new antimetabolite antibiotic, U-42,126, was discovered by use of a specific in vitro screen. U-42,126 was produced by the fermentation of
Streptomyces sviceus
. Its antimicrobial activity in vitro was limited to fungi. Certain bacteria were inhibited only when cultivated in completely synthetic media. U-42,126 was active in vivo against L1210 leukemia in mice.
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