Radicals and the role of ribonucleotide reductase

A wide range of iron chelators have been shown to inhibit ribonucleotide reductase [144-146] and this is likely to be the explanation of the cytotoxic properties of such molecules. Some iron chelators may also function as free radical scavengers. For instance, hydroxyurea appears to inhibit the enzyme by this latter mode of action [144], Such inhibitory agents block the cell division cycle in the S-phase because replication of cellular DNA is arrested. This also suggests possible therapeutic applications. 

Desferrioxamine and several related iron chelators have been demonstrated to inhibit the proliferation of a variety of malignant cell lines [148,149] as well proving inhibitory in acute neonatal leukaemia [150]. In addition desferrioxamine also exhibits in vivo anti-malarial activity in both humans and rats [151,152], Iron chelators have also been used to treat the inflammatory skin disorder, psoriasis, where there is hyperproliferation of keratinocytes and T-lymphocytes [153,154], A general problem still to be overcome with a number of powerful iron chelators is their lack of cell specificity and thus general toxicity for example to bone marrow function [144], 

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