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  • Title: New tripodal hydroxypyridinone based chelating agents for Fe(III), Al(III) and Ga(III): Synthesis, physico-chemical properties and bioevaluation.
    Author: Grazina R, Gano L, Sebestík J, Amelia Santos M.
    Journal: J Inorg Biochem; 2009 Feb; 103(2):262-73. PubMed ID: 19062099.
    Abstract:
    Two new tris-hydroxypyridinone based compounds (KEMPPr(3,4-HP)(3) and KEMPBu(3,4-HP)(3)) have been developed and studied as strong sequestering agents for iron and the group III of metal ions, aimed as potential pharmacological applications on metal-chelation therapy. Their structure is based on the KEMP acid scaffold to which three 3-hydroxy-4-pyridinone chelating moieties are attached via two different size spacers. After the preparation and characterization of the compounds their physico-chemical properties were studied, in relation with their metal binding affinity and lipophilicity. The KEMPPr(3,4-HP)(3) ligand was also bioassayed to evaluate its in vivo metal sequestering capacity from most organs using an animal model overload with (67)Ga. These studies showed that, for both in solution and in vivo conditions, the compounds have higher metal chelating efficacy than Deferriprone, the commercially available iron chelator in medical application, thus some perspectives are envisaged as potential pharmaceutical drug candidates for chelating therapy.
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