Site-activated multifunctional chelator with acetylcholinesterase and neuroprotective-neurorestorative moieties for Alzheimer's therapy.

Abstract

A novel strategy to develop site-activated multifunctional chelators for targeting multiple etiologies of Alzheimer's disease is reported. The novel prochelator HLA20A with improved cytotoxicity shows little affinity for metal ions until it is activated by binding and inhibiting acetylcholinesterase (AChE), releasing an active chelator HLA20 that modulates amyloid precursor protein (APP) regulation and beta-amyloid (Abeta) reduction, suppresses oxidative stress, and passivates excess metal ions (Fe, Cu, and Zn) in the brain.

• Authors: Hailin Zheng, Moussa B H Youdim, Mati Fridkin
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 52 Issue 14 Pg. 4095-8 (Jul 23 2009) ISSN: 1520-4804 [Electronic] United States
• PMID: 19485411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chelating Agents
• Cholinesterase Inhibitors
• Hydroxyquinolines
• Metals
• Neuroprotective Agents
• Piperazines
• Prodrugs
• 5-((4-prop-2-ynylpiperazin-1-yl)methyl)quinolin-8-ol
• Acetylcholinesterase

Topics

• Acetylcholinesterase (metabolism)
• Alzheimer Disease (drug therapy)
• Animals
• Brain (drug effects, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chelating Agents (chemistry, pharmacology, toxicity)
• Cholinesterase Inhibitors (chemistry, pharmacology, toxicity)
• Drug Design
• Humans
• Hydroxyquinolines (chemistry, pharmacology, therapeutic use, toxicity)
• Metals (chemistry)
• Neuroprotective Agents (chemistry, pharmacology, toxicity)
• Piperazines (chemistry, pharmacology, therapeutic use, toxicity)
• Prodrugs (chemistry, pharmacology, toxicity)
• Rats