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Iron chelators for the treatment of iron overload disease: Relationship between structure, redox activity, and toxicity
Author(s) -
Chaston Timothy B.,
Richardson Des R.
Publication year - 2003
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.10348
Subject(s) - toxicity , chelation , bioavailability , deferoxamine , chemistry , deferasirox , deferiprone , chelation therapy , intracellular , pharmacology , biochemistry , thalassemia , biology , medicine , inorganic chemistry , organic chemistry
Abstract 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.