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.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Acetylcholinesterase / metabolism*
- Alzheimer Disease / drug therapy*
- Animals
- Brain / drug effects
- Brain / metabolism
- Cell Line, Tumor
- Cell Survival / drug effects
- Chelating Agents / chemistry*
- Chelating Agents / pharmacology*
- Chelating Agents / toxicity
- Cholinesterase Inhibitors / chemistry
- Cholinesterase Inhibitors / pharmacology*
- Cholinesterase Inhibitors / toxicity
- Drug Design
- Humans
- Hydroxyquinolines / chemistry
- Hydroxyquinolines / pharmacology*
- Hydroxyquinolines / therapeutic use
- Hydroxyquinolines / toxicity
- Metals / chemistry
- Neuroprotective Agents / chemistry
- Neuroprotective Agents / pharmacology*
- Neuroprotective Agents / toxicity
- Piperazines / chemistry
- Piperazines / pharmacology*
- Piperazines / therapeutic use
- Piperazines / toxicity
- Prodrugs / chemistry
- Prodrugs / pharmacology
- Prodrugs / toxicity
- Rats
Substances
- Chelating Agents
- Cholinesterase Inhibitors
- Hydroxyquinolines
- Metals
- Neuroprotective Agents
- Piperazines
- Prodrugs
- 5-((4-prop-2-ynylpiperazin-1-yl)methyl)quinolin-8-ol
- Acetylcholinesterase