title: 1-(2-Hydroxyethoxy) methyl-2-methyl-3-hydroxyl-4-pyridinone: a targeted, 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.
authors: Radiobiology Division, Department of Radiology,University of Utah, Salt Lake City, Utah 84108, USA. gang.liu@hsc.utah.edu
authors: Gang
authors: G
authors: Liu
authors: Ping
authors: P
authors: Men
authors: Gerry H
authors: GH
authors: Kenner