Two pyridine derivatives as potential Cu(II) and Zn(II) chelators in therapy for Alzheimer's disease

Two pyridine derivatives, DMAP and ENDIP, have been investigated as possible metal chelators in the therapy of Alzheimer's disease. Their complex formation with Cu(ii) and Zn(ii) were characterised in detail. In the case of ENDIP a high stability tetradentate ML complex is formed at physiological pH both with Cu(ii) and Zn(ii). DMAP was found to be a weaker metal binder. At physiological pH, it forms a bidentate ML complex with Zn(ii) and MLH(-1) and ML(2) complexes with Cu(ii), depending on the metal ion to ligand ratio. Fluorescence spectroscopy and dynamic light scattering measurements proved that ENDIP effectively competes with aggregated amyloid-beta peptides (Abeta) for both Cu(ii) and Zn(ii) and thus is able to prevent the metal ion-induced amyloid aggregation and to resolubilise amyloid precipitates.