Novel iron chelators for iron overload disease and cancer treatment

Iron (Fe) chelation therapy involves the use of drugs that avidly bind Fe from biological systems. Iron chelators were developed for the treatment of Fe overload diseases, B-thalassemia and Friedreich's ataxia. However, the increased requirement for Fe in rapidly proliferating cancer cells, compared to normal cells, makes Fe a target for cancer chemotherapy. Iron chelators remove Fe from Fe-containing proteins, including ribonucleotide reductase, a key enzyme involved in the rate-limiting step of DNA synthesis and inhibit proliferation. Chelators with potent antiproliferative activity also demonstrate the ability to form Fe complexes that redox cycle. This leads to the generation of reactive oxygen species which induce DNA oxidation and mitochondrial damage. The investigations described in this book detail several structural features involved in targeting ligands for either the treatment of Fe overload disease or cancer chemotherapy. These findings emphasise the importance of donor atom identity and inductive effects on the redox cycling and antiproliferative activity of aroylhydrazone, thiohydrazone and thiosemicarbazone Fe chelators.

Autorentext

Danuta S. Kalinowski, B.Sc. (Hons), Ph.D.: Cancer Institute Early Career Development Fellow, University of Sydney, Sydney, Australia.Des R. Richardson, B.Sc., M.Sc., Ph.D., D.Sc: Professor of Cancer Cell Biology, NHMRC Senior Principal Research Fellow, Director of Iron Metabolism and Chelation Program, University of Sydney, Sydney, Australia.