Current Medicinal Chemistry - Volume 10, Issue 12, 2003

The occurrence of in vivo iron toxicity in the human body can be categorized into iron overload and non-iron overload conditions. Iron overload conditions are common in β-thalassemia and hereditary hemochromatosis patients, and anthracycline mediated cardiotoxicity is an example of a non-iron overload condition in cancer patients, in which the toxicity is iron-dependent.While hundreds of iron chelators have been evalua Read More

Iron is a metal of capital importance in most living organisms. However, man differs from the rest of mammals by his incapacity to excrete significant amounts of iron. This means that both iron deficiency and iron overload are frequently encountered. We briefly review our current understanding of dietary iron absorption and then discuss iron transport and delivery to cells. The intracellular storage and utilisation of i Read More

‘Iron chelation’ is widely understood as synonymous with non-specificity and viewed as a purely physicochemical mode of action, without any defined biomolecular target, broadly interfering with metalloenzymes. The 2-oxoacid-utilizing dioxygenases challenge this preconception. A family of non-heme iron enzymes that rely on chelation-dependent catalysis, they employ common molecules like Krebs cycle intermediates as Read More

This review focuses on advances and strategies in the use of iron chelators as anti-tumor therapies. Although the development of iron chelators for human disease has focused primarily on their use in the treatment of secondary iron overload, chelators may also be useful anti-tumor agents. They can deplete iron or cause oxidative stress in the tumor due to redox perturbations in its environment. Iron chelators have been tes Read More

The chelator currently used to treat iron (Fe) overload disease, desferrioxamine (DFO), has shown anti-proliferative activity against leukemia and neuroblastoma cells in vitro, in vivo and in clinical trials. Collectively, these studies suggest that Fe-deprivation may be a useful anti-cancer strategy. However, the efficacy of DFO is severely limited due to its poor ability to permeate cell membranes and bind intracellular Fe pools. Thes Read More

Deferiprone, a hydroxypyridin-4-one, is effective at facilitating iron removal from iron overloaded patients, when administered orally. Some problems associated with deferiprone are discussed. Hydroxypyridinone analogues with improved distribution, metabolism and affinity for iron are described. In particular the “high pFe3+”hydroxypyridin-4-ones possess considerable clinical potential.

Successful treatment of ß-thalassemia requires two key elements: blood transfusion and iron chelation. Regular blood transfusions considerably expand the lifespan of patients, however, without the removal of the consequential accumulation of body iron, few patients live beyond their second decade. In 1963, the introduction of desferrioxamine (DFO), a hexadentate chelator, marked a breakthrough in the treatment of Read More

The interest in synthetic siderophore mimics includes therapeutic applications (iron chelation therapy), the design of more effective agents to deliver Fe to plants and the development of new chemical tools for studies of iron metabolism and for a better understanding of iron assimilation processes in living systems. The 8-hydroxyquinoline bidentate chelate moiety offers an alternative to the usual hydroxamic acid, catech Read More