Future of ToxicologyIron Chelators and Differing Modes of Action and Toxicity:  The Changing Face of Iron Chelation Therapy

Danuta S. Kalinowski and Des R. Richardson*
Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia
Chem. Res. Toxicol., 2007, 20 (5), pp 715–720
DOI: 10.1021/tx700039c
Publication Date (Web): April 3, 2007
Copyright © 2007 American Chemical Society
*

 Corresponding author. Phone:  +61-2-9036-6548. Fax:  +61-2-9036-6549. E-mail:  d.richardson@med.usyd.edu.au.

Abstract

Abstract Image

Iron (Fe) chelation therapy was initially designed to alleviate the toxic effects of excess Fe evident in Fe-overload diseases. However, the novel toxicological properties of some Fe chelator−metal complexes have shifted appreciable focus to their application in cancer chemotherapy. Redox-inactive Fe chelator complexes are well suited for the treatment of Fe-overload diseases, whereas Fe chelator complexes with high redox activity have shown promising results as chemotherapeutics against cancer. Within this perspective, we discuss the different modes of action and toxicological profiles of Fe chelators, including analogues of 2-pyridylcarboxaldehyde isonicotinoyl hydrazone, di-2-pyridylketone isonicotinoyl hydrazone, di-2-pyridylketone thiosemicarbazone, and the clinically trialed chelator 3-aminopyridine-2-carboxaldehyde thiosemicarbazone. The potential application of these agents in the changing face of Fe chelation therapy is discussed.

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History

  • Published In Issue May 21, 2007
  • Received February 3, 2007

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