The essential role of anthraquinones as substrates for NADH dehydrogenase in their redox cycling activity.

Redox potential, superoxide production and NADH dehydrogenase substrate properties of daunorubicin, its four sugar-modified derivatives, 4-demethoxydaunorubicin and ametantrone have been examined. A new method for the determination of substrate properties of anthraquinones for NADH dehydrogenase has been developed. This method is based on the ability of anthraquinones to decrease the amount of enzymatic cytochrome c reduction at low concentrations of NADH. The compounds examined stimulated oxygen radical formation in a very varied manner. However, they had very similar redox properties. On the other hand, the extent of the diminution of cytochrome c reduction by anthraquinones depended strongly on the structure of the compounds examined. We postulate that it is not the redox properties but the enzyme substrate properties of anthraquinones which play the most important role in stimulating free radical formation.