1. Synthesis of aminoalkyl-substituted coumarin derivatives as acetylcholinesterase inhibitors.
- Author
-
Nam SO, Park DH, Lee YH, Ryu JH, and Lee YS
- Subjects
- Acetylcholinesterase metabolism, Animals, Cholinesterase Inhibitors pharmacology, Cholinesterase Inhibitors therapeutic use, Coumarins pharmacology, Coumarins therapeutic use, Disease Models, Animal, Enzyme Activation drug effects, Male, Memory drug effects, Memory Disorders chemically induced, Memory Disorders drug therapy, Mice, Mice, Inbred ICR, Protein Binding, Pyrrolidines chemistry, Pyrrolidines pharmacology, Pyrrolidines therapeutic use, Scopoletin chemistry, Scopoletin pharmacology, Scopoletin therapeutic use, Structure-Activity Relationship, Acetylcholinesterase chemistry, Cholinesterase Inhibitors chemical synthesis, Coumarins chemical synthesis, Coumarins chemistry, Pyrrolidines chemical synthesis
- Abstract
Alzheimer's disease, one of the most common forms of dementia, is a progressive neurodegenerative disorder symptomatically characterized by declines in memory and cognitive abilities. To date, the successful therapeutic strategy to treat AD is maintaining levels of acetylcholine by inhibiting acetylcholinesterase (AChE). In the present study, coumarin derivatives were designed and synthesized as AChE inhibitors based on the lead structure of scopoletin. Of those synthesized, pyrrolidine-substituted coumarins 3b and 3f showed ca. 160-fold higher AChE inhibitory activities than scopoletin. These compounds also ameliorated scopolamine-induced memory deficit in mice when administered orally at the dose of 1 and 2 mg/kg., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF