Back to Search
Start Over
Iron binding capacity of didox (3,4 dihydroxybenzohydroxamic acid) and amidox (3,4 dihydroxybenzamidoxime) two inhibitors of the enzyme ribonucleotide reductase.
- Source :
-
Advances in experimental medicine and biology [Adv Exp Med Biol] 1998; Vol. 431, pp. 599-604. - Publication Year :
- 1998
-
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 circumvented by addition of Fe-ammoniumcitrate, indicating the iron complexing capacity not to 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, only slight 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 an iron complex, but in contrast to other agents, the anticancer activity cannot be contributed to this effect alone. Further studies will have to elucidate the molecular mechanism of action of these new and promising anticancer agents.
- Subjects :
- Animals
Antineoplastic Agents toxicity
Cell Division drug effects
Enzyme Inhibitors toxicity
Humans
Hydroxamic Acids toxicity
Iron pharmacology
Leukemia L1210
Mice
Oximes toxicity
Polarography
Tumor Cells, Cultured
Antineoplastic Agents chemistry
Enzyme Inhibitors chemistry
Hydroxamic Acids chemistry
Iron chemistry
Oximes chemistry
Ribonucleotide Reductases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0065-2598
- Volume :
- 431
- Database :
- MEDLINE
- Journal :
- Advances in experimental medicine and biology
- Publication Type :
- Academic Journal
- Accession number :
- 9598136
- Full Text :
- https://doi.org/10.1007/978-1-4615-5381-6_116