Siderophores chelation treatments

Isol. from Streptomyces pilosus. Siderophore. Chelating agent for iron mobilization used as antidote to iron poisoning also chelates aluminium, of interest with respect to treatment of Alzheimer s disease. Used as 4mAf aq. soln. for photometric detn. of V(F) 480 nm, 3150, pH 1.3), Fe(///). Cryst. -I- IH2O (EtOH aq.). Mp 138-140°. 

Chelators of iron, which are now widely applied for the treatment of patients with thalassemia and other pathologies associated with iron overload, are the intravenous chelator desferal (desferrioxamine) and oral chelator deferiprone (LI) (Figure 19.23, see also Chapter 31). Desferrioxamine (DFO) belongs to a class of natural compounds called siderophores produced by microorganisms. The antioxidant activity of DFO has been studied and compared with that of synthetic hydroxypyrid-4-nones (LI) and classic antioxidants (vitamin E). It is known that chronic iron overload in humans is associated with hepatocellular damage. Therefore, Morel et al. [370] studied the antioxidant effects of DFO, another siderophore pyoverdin, and hydroxypyrid-4-ones on lipid peroxidation in primary hepatocyte culture. These authors found that the efficacy of chelators to inhibit iron-stimulated lipid peroxidation in hepatocytes decreased in the range of DFO > hydroxypyrid-4-ones > pyoverdin. It seems that other siderophores are also less effective inhibitors of lipid peroxidation than DFO [371],... 

Desferrioxamine (DFO-B), the natural siderophore initially isolated from Streptomyces pilosus, is the only iron chelator currently used for clinical treatment of iron-overload disease such as thalassemia, sickle cell anemia and hemochromatosis ° . ... 

Conventional treatments for hemochromatosis and for nutritional iron overload include reduction of dietary iron and periodic removal of blood (phlebotomy) until iron stores are reduced. In transfusion siderosis, it is necessary to eliminate iron via the urine by the intravenous infusion of highly specific chelating agents such as desferral (see Iron Transport Siderophores). This process is painful, laborious, and costly. The development of new orally effective iron chelators is expected. 

Infection risk Iron is an essential nutrient in many species, and iron overload increases the risk of infections. Deferoxamine is a natural siderophore, and its use is a susceptibility factor for infections with a variety of microbes, notably Yersinia enterocolitica and Mucorales infections, and increases their infectivity. On the other hand, iron chelators, by extracting iron, may also have cm anti-infectious action, which may be therapeutically beneficial, in particular in the treatment of malaria (deferiprone) [4 ] or mucormycosis (deferasirox) [5 ]. While the use of iron-chelating drugs is currently being further investigated, for the... 

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