DIMINISHED SUPEROXIDE ANION GENERATION BY REDUCED 5-IMINODAUNORUBICIN RELATIVE TO DAUNORUBICIN AND THE RELATIONSHIP TO CARDIOTOXICITY OF THE ANTHRACYCLINE ANTI-TUMOR AGENTS .18.

5-Iminodaunorubicin, when reductively activated, produces single strand scission in PM2-CCC-DNA by a mechanism which proceeds via production of Superoxide anion and hydroxyl radicals. Under comparable conditions, 5-iminodaunorubicin produces much less nicking than daunorubicin. With the aid of N-cyclohexyl-5-iminoquinizarin, as a model, assignment of polarographic waves to the quinone moiety of 5-iminodaunorubicin was possible. The electrochemical results indicate that 5-iminodaunorubicin is more difficult to reduce than daunorubicin and that reoxidation of the reduced form, 5,11-dihydro-5-iminodaunorubicin, is much more difficult than reoxidation of reduced daunorubicin. The latter conclusion is supported by independent chemical studies. By comparison of 5-iminodaunorubicin with daunorubicin and N-cyclohexyl-5-iminoquinizarine, the unusual stability of the reduced 5-iminodaunorubicin, is tentatively attributed to strong hydrogen bonding. The results suggest a correlation between the diminished generation of Superoxide anion by 5-iminodaunorubicin and its observed suppressed cardiotoxicity relative to other anthracyclines. © 1979.