[The ribonucleotide reductase enzyme as a target for enzyme-directed chemotherapy effects of trimidox (3,4,5-trihydroxybenzohydroxamidoxim), a new inhibitor of ribonucleotide reductases].
Inhibition of the enzyme ribonucleotide reductase by polyhydroxy-substituted benzohydroxamide derivates is an example for the effects of antimetabolites. 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 inhibits the enzyme in cell extracts as well as in the in situ assay and causes decreased dGTP and dCTP pools in HL-60 cells. We describe combinations with other antimetabolites, as well as biochemical, morphological and cytotoxic effects of trimidox. This manuscript gives an overview of our results with trimidox and describes selection criteria, effects and combinations used in enzyme-targeted chemotherapy.
Institut für Medizinische Chemie, Universität Wien.
G
G
Findenig
E
E
Vielnascher
R
R
Göbl
M
M
Fritzer-Szekeres
T
T
Szekeres
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001550:Benzamidines / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
C074761:3,4,5-trihydroxybenzamidoxime; D000964:Antimetabolites, Antineoplastic; D001550:Benzamidines; D004791:Enzyme Inhibitors; D012264:Ribonucleotide Reductases
Das Enzym Ribonukleotid-Reduktase als Target für enzymgerichtete Chemotherapie-Wirkungen von Trimidox (3,4,5-Trihydroxybenzohydroxamidoxim), einem neuen Inhibitor der Ribonukleotid-Reduktase.