A series of potential drugs for patients suffering from iron-overload disorders show unusual iron binding properties, say researchers in Australia.

Paul Bernhardt, Des Richardson from the Universities of Queensland and Sydney and their colleagues, studied iron-binding ligands based on nicotinyl hydrazone.  'These ligands are an emerging class of iron-binding drugs that show great promise for the treatment of iron overload diseases,' said Bernhardt. One hydrazone ligand has already been shown to be orally active for treating iron overload in mice, he said.

'Humans are especially susceptible to iron overload as they have no natural mechanism for iron excretion,' Bernhardt explained. In excess, iron can generate harmful oxygen species, damaging membranes, proteins and DNA. Sufferers of iron overload must undergo chelation therapy, in which drug ligands bind to the iron and allow it to be removed by excretion. 

The Australian group showed that the new ligands bind to iron(II), as opposed to the iron(III) absorbed by most other iron-binding drugs. As a result, Bernhardt asserted, the ligands 'do not compete with the more effective iron(III) binding proteins in the body, but are able to target divalent iron(II). They are effective at both reducing iron uptake and mobilisation by cells, which could be related to their ability to intercept iron after its release from within the cell.' 

Currently, the most widely-used iron-binding drug is Desferal (deferoxamine mesylate), but it is not only expensive but poorly-absorbed when administered orally and must be delivered by an infusion pump, leading to poor patient compliance. Kathryn Robson of the University of Oxford in the UK, who works in the field of iron overload disorders, suggested that the new ligands could be a useful alternative. 'Any new iron chelators have to be safe, cheap and must be administered orally,' she said. 'These ligands provide a novel approach to the development of new drugs and may prove cost-effective for use in developing countries.'

Michael Spencelayh