CC-1065 (NSC-298223), a new antitumor antibiotic. Production, in vitro biological activity, microbiological assays and taxonomy of the producing microorganism.
نویسندگان
چکیده
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 approximately 10 ng/ml, while these values for Gram-negative bacteria and fungi are mostly under 1 microgram/ml. A microbiological assay with Bacillus subtilis can detect concentrations of 1 approximately 2 ng/ml.
منابع مشابه
The chemistry, mechanism of action and biological properties of CC-1065, a potent antitumor antibiotic.
The structure of CC-1065 (Fig. 1) was determined by X-ray crystallography5,6). Prior to isolation of a suitable crystalline form of CC-1065 for X-ray diffraction data collection, a chemical degradation product (1) obtained by reaction of CC-1065 with ethyl isocyanate in pyridine was crystallized and its structure determined by X-ray crystallography". A closely related compound, PDE I (2), was p...
متن کاملMechanism of interaction of CC-1065 (NSC 298223) with DNA.
CC-1065 (NSC 298223), a potent new antitumor antibiotic produced by Streptomyces zelensis, interacts strongly with double-stranded DNA and appears to exert its cytotoxic effects through disruption of DNA synthesis. We undertook this study to elucidate the sites and mechanisms of CC-1065 interaction with DNA. The binding of CC-1065 to synthetic and native DNA was examined by differential circula...
متن کاملGilvusmycin, a new antitumor antibiotic related to CC-1065.
A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp. QM16. The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis. Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo.
متن کاملThe Azinomycins. Discovery, Synthesis, and DNA-Binding Studies
Nature is a rich source of potential antitumor agents that can act as a paradigm for the development of synthetic agents that retain the biological activity of the natural product but are targeted to the tumor, have increased bioavailability or are simply prodrug forms that are inactive until administered. Examples of potent antitumor antibiotics that interact with DNA include the clinically us...
متن کاملInteraction of CC-1065 and its analogues with mouse DNA and chromatin.
CC-1065 is a potent antitumor antibiotic which is cytotoxic to P388 and L1210 leukemia cells in vitro and in vivo. CC-1065 covalently binds to calf thymus DNA preferentially to adenine-thymine regions at N3 of adenine. Here, we compare CC-1065 interaction with P388-derived chromatin, DNA, and histones as measured by electronic absorption and circular dichroism. Two CC-1065 analogues (U-71,184 a...
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ورودعنوان ژورنال:
- The Journal of antibiotics
دوره 31 12 شماره
صفحات -
تاریخ انتشار 1978