THE ENZYME RIBONUCLEOTIDE REDUCTASE - TARGET FOR ANTITUMOR AND ANTI-HIV THERAPY

Ribonucleotide reductase is the rate-limiting enzyme of DNA synthesis, and it has been shown to be linked with malignant transformation and tumor cell proliferation. It was therefore considered as an excellent target for cancer chemotherapy. This article reviews the in vitro and in vivo effects of hydroxyurea the first inhibitor of the enzyme, whic h is currently used in general clinical practice. In addition, we summ arize the results obtained with other inhibitors of the enzyme; for in stance, polyhydroxy-substituted benzohydroxamic acid derivatives, a pr omising group of inhibitors of ribonucleotide reductase that was synth esized by Bart van'T Riet and investigated by our group. In vitro as w ell as animal data and pharmacokinetic results are reviewed and possib le implications for an improvement in the management of various patien t groups ate outlined.