1-(2-Hydroxyethoxy)Methyl-2-Methyl-3-Hydroxyl-4-Pyridinone: ATargeted, Bifunctional Chelating Agent for Potential Uranic Detoxification in the Kidney

Abstract

The only proposed treatment for uranium (U) internal decontamination is chelation therapy, and so far, there is no effective chelating drug available for this purpose. A modified iron chelator of deferiprone (L1) has been investigated for its chemical and pharmacological properties as a new U chelating agent. The results have demonstrated that the chelator, 1-(2-hydroxyethoxy)methyl-2-methyl-3-hydroxyl-4-pyridinone (HEML1), has the ability to chelate uranyl ion, forming a stable complex with 2:1 (chelator/U) stoichiometry. The chelator, HEML1, does not pose any adverse effects on cultured human kidney cells, and shows the capability of protecting the cells against U-associated cytotoxicity and hydrogen peroxide-induced free radical damage. Moreover, because of the hydrophilic property of both HEML1 and its U-complex, the chelator has the potential to target the kidneys where the U prefer to deposit, and to leave the organ after complexing U. These results suggest that HEML1 may be able to serve as a bifunctional therapeutic for internal radionuclide decontamination.

• Internal radionuclide contamination
• Uranium (U) toxicity
• Chelation agent
• Targeted detoxification
• Oxidative damage