IRON CHELATING-AGENTS WITH CLINICAL POTENTIAL

Iron is a critically important metal for a wide variety of cellular events. The element holds this central position by virtue of its facile redox chemistry and the high affinity of both redox states (iron II and iron III) for oxygen. These same properties also render iron toxic when levels exceed the normal binding capacity of the cell. As a result of this potential toxicity, selective iron chelators are finding an important role in the treatment of iron overload associated with many forms of thalassaemia. In addition, they appear to have potential in treating situations where a local increase in iron concentration causes an unfavourable pathology, for instance, in reperfused tissue (heart disease and stroke) and in Parkinsonian brain. There is also evidence that iron chelators may minimise the toxicity of paraquat and the side effects of bleomycin and doxorubicin. Non-haem iron enzymes can also be inhibited by iron chelators and consequently such enzymes as ribonucleotide reductase and lipoxygenase can be selectively inhibited. Such inhibitory action is being investigated for the treatment of malaria, neoplastic disease, psoriasis and asthma. Recent developments in these areas are discussed in the present overview.