1-(2-HYDROXYETHOXY)METHYL-2-METHYL-3-HYDROXYL-4-PYRIDINONE: A TARGETED, BIFUNCTIONAL CHELATING AGENT FOR POTENTIAL URANIC DETOXIFICATION IN THE KIDNEY

作者：Liu Gang^*; Men Ping; Kenner Gerry H

来源：Hemoglobin, 2011, 35(3): 291-300.

DOI：10.3109/03630269.2011.563713

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

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.

• 出版日期2011