RIBONUCLEOTIDE REDUCTASE AS TARGET FOR EN ZYME-DIRECTED CHEMOTHERAPY-EFFECTS OF TRIMIDOX (3,4,5-TRIHYDROXYBENZOHYDROXIME), A NEW INHIBITOR OF RIBONUCLEOTIDE REDUCTASE

Inhibition of the enzyme ribonucleotide reductase by polyhydroxy-subst ituted benzohydroxamide derivates is an example for the effects of ant imetabolites. We present an overview of the effects of antimetabolites , in particular regarding their action on leukemia cells, Trimidox is one of the most effective inhibitors of ribonucleotide reductase. It i nhibits the enzyme in cell extracts as well as in the in situ assay an d causes decreased dGTP and dCTP pools in KL-60 cells. We describe com binations with other antimetabolites, as well as biochemical, morpholo gical and cytotoxic effects of trimidox. This manuscript gives an over view of our results with trimidox and describes selection criteria, ef fects and combinations used in enzyme-targeted chemotherapy.