IRON-BINDING-CAPACITY OF DIDOX (3,4-DIHYDROXYBENZOBYDROXAMIC ACID) AND AMIDOX (3,4-DIHYDROXYBENZAMIDOXIME) NEW INHIBITORS OF THE ENZYME RIBONUCLEOTIDE REDUCTASE

Ribonucleotide reductase is the rate limiting enzyme of deoxynucleosid e triphosphate synthesis and is considered to be an excellent target o f cancer chemotherapy. Didox and amidox are newly synthesized compound s, which inhibit this enzyme and have in vitro and in vivo antitumor a ctivity. We have now investigated the capability of didox and amidox t o interfere with the iron metabolism. We show by photometric and polar ographic methods, that didox and amidox are capable of forming an iron complex. However, their cytotoxic action cannot be completely circumv ented by addition of Fe-ammoniumcitrate, indicating that the iron comp lexing capacity may not be responsible for the mechanism of action of these compounds. When L1210 leukemia cells were incubated with the did ox-iron or amidox-iron complex itself, changes of the 50% growth inhib itory capacity of the complex in comparison with didox or amidox alone could be shown. We conclude, that didox and amidox are capable of for ming iron complexes, but in contrast to other agents, the anticancer a ctivity cannot be contributed to this effect alone. Future studies wil l have to elucidate the molecular mechanism of action of these new and promising anticancer agents.