A new antitumor antibiotic: Demethylstreptonigrin.

The Journal of Antibiotics
1986.0

Abstract

In our screening for antitumor antibiotics inhibiting the growth of resistant P388 leukemia cells, a streptomyces strain MG883-12F2 was selected. We found that this strain produced streptonigrin (2)1). Furthermore we discovered a new analog which has been determined to be 10'-O-demethylstreptonigrin (1). This strain was classified as Streptornyces afbits.It has been reported that streptonigrin has strong antitumor activity against a variety of tumors but extremely strong toxicity'',3>. Several studies on streptonigrin structure-activity relationships have been reported and the synthesis of its analogs having high antitumor activity and low toxicity has been attempted. In this paper, the isolation and structure determination by means of NMR and physico-chemical properties of demethylstreptonigrin are reported. Streptonigrin (2) is known to be active against Gram-positive and Gram-negative bacteria but demethylstreptonigrin (1) has only weak antibacterial activity. The cytotoxic activities (50 % inhibition concentrations) of 2 and 1 on P388 leukemia cells in vitro are 0.025 i g/ml and 0.58 tag/ml, respectively. On P388 resistant to adriamycin, those of 2 and 1 are 0.01 tag/ml and 0.41 l'g/ml, respectively.

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