In vitro studies of 3-hydroxy-4-pyridinones and their glycosylated derivatives as potential agents for Alzheimer's disease.
|Title||In vitro studies of 3-hydroxy-4-pyridinones and their glycosylated derivatives as potential agents for Alzheimer's disease.|
|Publication Type||Journal Article|
|Year of Publication||2010|
|Authors||Green DE, Bowen ML, Scott LE, Storr T, Merkel M, Boehmerle K, Thompson KH, Patrick BO, Schugar HJ, Orvig C|
|Pagination||1604 - 1615|
|Keywords||hydroxypyridinone Alzheimers disease|
Glycosides of 3-hydroxy-4-pyridinones were synthesized and characterized by mass spectrometry, elemental anal., 1H and 13C NMR spectroscopy, and in one case by X-ray crystallog. The Cu2+ complex of a novel 3-hydroxy-4-pyridinone was synthesized and characterized by IR and X-ray crystallog., showing the ability of these compds. to chelate potentially toxic metal ions. An MTT cytotoxicity assay of a selected glycosylated compd. showed a relatively low toxicity of IC50 = 570 ± 90 μM in a human breast cancer cell line. The pyridinone glycosides could be cleaved by a broad specificity beta-glycosidase, Agrobacterium sp.β-glucosidase, and for one compd. kcat and Km were detd. to be 19.8 s-1 and 1.52 mM, resp. Trolox Equiv. Antioxidant Capacity (TEAC) values were detd. for the free pyridinones, indicating the good antioxidant properties of these compds. Metal-Aβ1-40 aggregates with zinc and copper were resolubilized by the non-glycosylated pyridinone ligands. [on SciFinder(R)]