In vitro studies of 3-hydroxy-4-pyridinones and their glycosylated derivatives as potential agents for Alzheimer's disease

Glycosides of 3-hydroxy-4-pyridinones were synthesized and characterized by mass spectrometry, elemental analysis, (1)H and (13)C NMR spectroscopy, and in one case by X-ray crystallography. The Cu(2+) complex of a novel 3-hydroxy-4-pyridinone was synthesized and characterized by IR and X-ray crystallography, showing the ability of these compounds to chelate potentially toxic metal ions. An MTT cytotoxicity assay of a selected glycosylated compound showed a relatively low toxicity of IC(50) = 570 +/- 90 microM in a human breast cancer cell line. The pyridinone glycosides could be cleaved by a broad specificity beta-glycosidase, Agrobacterium sp.beta-glucosidase, and for one compound k(cat) and K(m) were determined to be 19.8 s(-1) and 1.52 mM, respectively. Trolox Equivalent Antioxidant Capacity (TEAC) values were determined for the free pyridinones, indicating the good antioxidant properties of these compounds. Metal-Abeta(1-40) aggregates with zinc and copper were resolubilized by the non-glycosylated pyridinone ligands.