Studies related to antitumor antibiotics. Part VIII. Cleavage of DNA by streptonigrin analogues and the relationship to antineoplastic activity.
A group of substituted 5,8-quinolinequinones which exhibit antineoplastic activity and which are structurally related to the antitumor antibiotic streptonigrin induce single strand cleavage of PM2 covalently-closed circular-DNA (ccc-DNA) when reductively activated. The cleavage which is detected by an ethidium fluorescence assay is specifically enhanced by cuprous and ferrous ion and is selectively inhibited by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) and by free radical scavengers. Independent generation of the superoxide ion by xanthine-xanthine oxidase (EC 1.2.3.2) also cleaves PM2 DNA and therefore a chemical mechanism for the scission process induced by the streptonigrin analogues is formulated. A correlation between rate of PM2 ccc-DNA cleavage and inhibition of Walker carcinosarcoma 256 is observed.
D000818:Animals; D001435:Bacteriophages; D001665:Binding Sites; D004277:DNA, Single-Stranded; D004279:DNA, Viral; D007700:Kinetics; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011549:Pseudomonas; D013308:Streptonigrin / Q000031:analogs & derivatives* / Q000627:therapeutic use
D004277:DNA, Single-Stranded; D004279:DNA, Viral; D013308:Streptonigrin