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Iron chelators for the treatment of iron overload disease: Relationship between structure, redox activity, and toxicity
Timothy B. Chaston,
Des R. Richardson,
Timothy B. Chaston
Children's Cancer Institute Australia for Medical Research, The Iron Metabolism and Chelation Program, Randwick, Sydney, New South Wales, Australia
Search for more papers by this authorCorresponding Author
Des R. Richardson
Children's Cancer Institute Australia for Medical Research, The Iron Metabolism and Chelation Program, Randwick, Sydney, New South Wales, Australia
Children's Cancer Institute Australia for Medical Research, Iron Metabolism and Chelation Program, P.O. Box 81, High St., Randwick, Sydney, New South Wales, 2031 AustraliaSearch for more papers by this authorTimothy B. Chaston,
Des R. Richardson,
Timothy B. Chaston
Children's Cancer Institute Australia for Medical Research, The Iron Metabolism and Chelation Program, Randwick, Sydney, New South Wales, Australia
Search for more papers by this authorCorresponding Author
Des R. Richardson
Children's Cancer Institute Australia for Medical Research, The Iron Metabolism and Chelation Program, Randwick, Sydney, New South Wales, Australia
Children's Cancer Institute Australia for Medical Research, Iron Metabolism and Chelation Program, P.O. Box 81, High St., Randwick, Sydney, New South Wales, 2031 AustraliaSearch for more papers by this authorAbstract
The success of the iron (Fe) chelator desferrioxamine (DFO) in the treatment of β-thalassemia is limited by its lack of bioavailability. The design and characterization of synthetic alternatives to DFO has attracted much scientific interest and has led to the discovery of orally active chelators that can remove pathological Fe deposits. However, chelators that access intracellular Fe pools can be toxic by either inhibiting Fe-containing enzymes or promoting Fe-mediated free radical damage. Interestingly, toxicity does not necessarily correlate with Fe-binding affinity or with chelation efficacy, suggesting that other factors may promote the cytopathic effects of chelators. In this review, we discuss the interactions of chelators and their Fe complexes with biomolecules that can lead to toxicity and tissue damage. Am. J. Hematol. 73:200–210, 2003. © 2003 Wiley-Liss, Inc.
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