Further studies on the generation of reactive oxygen species from activated anthracyclines and the relationship to cytotoxic action and cardiotoxic effects.

The relative ease of generation of reactive oxygen species from a series of reductively activated aglycone and sugar modified anthracyclines was compared by the extents of single strand scission in supercoiled PM2-covalently closed circular (CCC)-DNA. The electrochemical properties of these agents were used as a quantitative measure of the ease of reduction and subsequent reoxidation of the reduced species. The relationship of these processes to various biological properties of the anthracyclines, in particular to the measured cardiotoxicity of the drugs, was examined. An attempt was made to identify those structural changes which ameliorate the cardiotoxic effects measured in other test systems while permitting the expression of antitumor properties.