Future of toxicology--iron chelators and differing modes of action and toxicity: the changing face of iron chelation therapy.
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.
Kalinowski
Danuta S
DS
Iron Metabolism and Chelation Program, Department of Pathology, University of Sydney, Sydney, New South Wales 2006, Australia.
Richardson
Des R
DR
D015913:Chelation Therapy; D006801:Humans; D006835:Hydrazones / Q000009:adverse effects* / Q000737:chemistry; D007502:Iron Chelating Agents / Q000009:adverse effects* / Q000737:chemistry; D019190:Iron Overload / Q000188:drug therapy* / Q000378:metabolism; D007538:Isoniazid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry; D011725:Pyridines / Q000009:adverse effects / Q000737:chemistry; D011730:Pyridoxal / Q000009:adverse effects / Q000031:analogs & derivatives / Q000737:chemistry; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000009:adverse effects / Q000737:chemistry; D014116:Toxicology
C404192:2-pyridylcarboxaldehyde isonicotinoylhydrazone; D006835:Hydrazones; D007502:Iron Chelating Agents; D011725:Pyridines; D013882:Thiosemicarbazones; C508927:di-2-pyridyl ketone N(4)-phenylthiosemicarbazone; C078157:3-aminopyridine-2-carboxaldehyde thiosemicarbazone; D011730:Pyridoxal; C021079:pyridoxal isonicotinoyl hydrazone; D007538:Isoniazid