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, which is currently used in general clinical practice. In addition, we summarize the results obtained with other inhibitors of the enzyme; for instance, polyhydroxy-substituted benzohydroxamic acid derivatives, a promising group of inhibitors of ribonucleotide reductase that was synthesized by Bart van'T Riet and investigated by our group. In vitro as well as animal data and pharmacokinetic results are reviewed and possible implications for an improvement in the management of various patient groups are outlined.
Szekeres
T
T
Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna Medical School, Austria.
Fritzer-Szekeres
M
M
Elford
H L
HL
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D006918:Hydroxyurea / Q000627:therapeutic use; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D012264:Ribonucleotide Reductases; D006918:Hydroxyurea