From antioxidant chelators to site-activated multi-target chelators targeting hypoxia inducing factor, beta-amyloid, acetylcholinesterase and monoamine oxidase A/B.
Chelators hold great promise as disease-modifying drugs for Alzheimer's therapy, and recent research efforts have focused on designing multi-target chelators with increased targeting and efficacy through rational drug design. In this review, we discuss our research studies on the rational design of new multi-target chelators with the potential not only to simultaneously modulate several disease-related targets, but also contain features designed to improve the BBB permeability, increase the brain targeting, and minimize potential side effects. These new chelators include neuroprotective chelators with brain selective monoamine oxidase (MAO) A/B inhibitory activity, acetylcholinesterase (AChE) inhibitors with site-activated chelating and neurogenesis activity, and AChE-MAO A/B inhibitors with site-activated chelating and neurogenesis activity.
Department of Medicinal Chemistry, Intra-cellular Therapies Inc., New York, NY 10032, USA. hailin20070109@hotmail.com
H
H
Zheng
M
M
Fridkin
M B H
MB
Youdim
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002614:Chelating Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002614:Chelating Agents; D051793:Hypoxia-Inducible Factor 1; D008995:Monoamine Oxidase; D000110:Acetylcholinesterase