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Iron binding capacity of didox (3,4-dihydroxybenzohydroxamic acid) and amidox (3,4-dihydroxybenzamidoxime) new inhibitors of the enzyme ribonucleotide reductase.
- Source :
-
Life sciences [Life Sci] 1997; Vol. 61 (22), pp. 2231-7. - Publication Year :
- 1997
-
Abstract
- Ribonucleotide reductase is the rate limiting enzyme of deoxynucleoside triphosphate synthesis and is considered to be an excellent target of cancer chemotherapy. Didox and amidox are newly synthesized compounds, which inhibit this enzyme and have in vitro and in vivo antitumor activity. We have now investigated the capability of didox and amidox to interfere with the iron metabolism. We show by photometric and polarographic methods, that didox and amidox are capable of forming an iron complex. However, their cytotoxic action cannot be completely circumvented by addition of Fe-ammoniumcitrate, indicating that the iron complexing capacity may not be responsible for the mechanism of action of these compounds. When L1210 leukemia cells were incubated with the didox-iron or amidox-iron complex itself, changes of the 50% growth inhibitory capacity of the complex in comparison with didox or amidox alone could be shown. We conclude, that didox and amidox are capable of forming iron complexes, but in contrast to other agents, the anticancer activity cannot be contributed to this effect alone. Future studies will have to elucidate the molecular mechanism of action of these new and promising anticancer agents.
- Subjects :
- Animals
Antineoplastic Agents toxicity
Enzyme Inhibitors toxicity
Humans
Hydroxamic Acids toxicity
Leukemia L1210 drug therapy
Leukemia, Erythroblastic, Acute drug therapy
Mice
Oxidation-Reduction
Oximes toxicity
Polarography
Tumor Cells, Cultured
Antineoplastic Agents metabolism
Antineoplastic Agents pharmacology
Enzyme Inhibitors metabolism
Enzyme Inhibitors pharmacology
Hydroxamic Acids metabolism
Hydroxamic Acids pharmacology
Iron Compounds metabolism
Oximes metabolism
Oximes pharmacology
Ribonucleotide Reductases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0024-3205
- Volume :
- 61
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 9393942
- Full Text :
- https://doi.org/10.1016/s0024-3205(97)00925-9