Competition between deferiprone, desferrioxamine and other chelators for iron and the effect of other metals.
Competition for iron between the leading oral iron chelator deferiprone (L1, 1,2-dimethyl-3-hydroxypyrid-4-one) and desferrioxamine (DF), and the effect of other metals has been studied. Visible spectroscopy was used to estimate the displacement of iron from DF-iron(III) and L1-iron(III) complexes, respectively, by varying quantities of up to 100 molar equivalent of a competing metal ion M+ (Mg2+, Al3+, Ca2+, Mn2+, Co2+, Cu2+, Zn2+ and Pb2+) at physiological pH. Copper and aluminium showed the greatest competition against iron, while magnesium, calcium and manganese had little or no effect and the other metals an intermediate effect. DF showed greater selectivity for iron than L1 under these conditions. An analogous series of experiments carried out using a competing chelator of up to 50 molar equivalent in a place of a competing metal ion showed that 8-hydroxyquinoline, diethylenetriamine-pentaacetic acid (DTPA) and tropolone were more effective at displacing iron from DF-Fe and (L1)3Fe complexes than maltol or omadine. Desferrioxamine was the most efficient competitor against L1. Stoichiometric studies of the L1 complexes of aluminium and copper at pH 7.4 using Job Plots, suggested the formation of (L1)3Al and (L1)2Cu complexes, respectively.
Sheppard
L N
LN
Department of Haematology, Royal Free Hospital School of Medicine, London, United Kingdom.
Kontoghiorghes
G J
GJ
D000535:Aluminum / Q000737:chemistry; D001667:Binding, Competitive / Q000187:drug effects; D003300:Copper / Q000737:chemistry; D000077543:Deferiprone; D003676:Deferoxamine / Q000737:chemistry / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D008670:Metals / Q000737:chemistry; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology*; D013053:Spectrophotometry
D007502:Iron Chelating Agents; D008670:Metals; D011728:Pyridones; D000077543:Deferiprone; D003300:Copper; D000535:Aluminum; D003676:Deferoxamine