Alzheimer's disease (AD) is a chronic and irreversible neurodegenerative illness, which involves the progressive deterioration of intellectual functions and behavioral disorders. Several therapeutic approaches have been proposed, but only four acetylcholinesterase inhibitors and one N-methyl-D-aspartate receptor antagonist have been approved by the US Food and Drug Administration, which have quite limited effectiveness and that mostly provide palliative therapy. The complex pathology of this multifaceted disease and the possible interconnections among numerous intervening factors have led to the development of several multi-target candidate drugs. This review describes the most recent progress in multifunctional. compounds containing a biometal (Fe, Cu, Zn) chelating unity for potential AD prevention/therapy. The importance of including a chelating moiety in these anti-AD drug candidates is associated with the recognized roles played by metal dyshomeostasis and related oxidative stress in AD pathogenesis, particularly by preceding or inducing the hallmark pathologies of this disease (neurofibrillary tangles, senile plaques, and reactive oxygen species). This review focuses on recent approaches based on the combination or fusion of different functions in a unique molecular entity, including chelating moieties, with various types of donor atoms and denticity in several scaffolds, i.e., 8-hydroxyquinolines, beta-aminopyridines and other diamino-based chelators, phenol-amino derivatives, amino/hydroxyl chalcones, 3-hydroxy-4-pyridinones, flavonoids, and hydroxyanthraquinones. (C) 2016 Elsevier B.V. All rights reserved.
展开▼
