The ability of new formamidine sugar-modified derivatives of daunorubicin to stimulate free radical formation in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase and xanthine oxidase

Some sterically hindered N-substituted derivatives of daunorubicin are know n to be poor substrates for NADH dehydrogenase, NADPH cytochrome P450 reduc tase and xanthine oxidase. In consequence, poor oxygen radical generation b y these compounds is observed. In this study we examined a new family of sugar-N-substituted derivatives o f daunorubicin bearing a bulky substituent introduced on the nitrogen atom through the amidine spacer. These compounds were found to be very active in radical formation catalyzed by all three studied enzymes. Thus, the introd uction of a heterocyclic ring, even if it is bulky but flexible, on the nit rogen atom of daunosamine moiety through the one-atom spacer (amidine group ), does not induce the steric hindrance effect on the interaction of daunor ubicin derivatives with these flavoprotein enzymes.