3-(4-[[Benzyl(methyl)amino]methyl]phenyl)-6,7-dimethoxy-2H-2-chromenone (AP2238) inhibits both acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation: a dual function lead for Alzheimer's disease therapy.

Abstract

In recent years, the investigation of acetylcholinesterase (AChE) inhibitors has gained further interest, because the involvement of the peripheral site of the enzyme in the beta-amyloid (Abeta) aggregation process has been disclosed. We present here, for the first time, a direct evidence of the Abeta antiaggregating action of an AChE inhibitor (AP2238) purposely designed to bind at both the catalytic and the peripheral sites of the human enzyme.

• Authors: Lorna Piazzi, Angela Rampa, Alessandra Bisi, Silvia Gobbi, Federica Belluti, Andrea Cavalli, Manuela Bartolini, Vincenza Andrisano, Piero Valenti, Maurizio Recanatini
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 46 Issue 12 Pg. 2279-82 (Jun 05 2003) ISSN: 0022-2623 [Print] United States
• PMID: 12773032 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AP 2238
• Amyloid beta-Peptides
• Benzopyrans
• Benzylamines
• Cholinesterase Inhibitors
• Coumarins
• Acetylthiocholine
• Acetylcholinesterase
• Butyrylcholinesterase

Topics

• Acetylcholinesterase (chemistry)
• Acetylthiocholine (chemistry)
• Alzheimer Disease (drug therapy)
• Amyloid beta-Peptides (chemistry)
• Benzopyrans (chemical synthesis, chemistry)
• Benzylamines (chemical synthesis, chemistry)
• Butyrylcholinesterase (chemistry)
• Catalytic Domain
• Cholinesterase Inhibitors (chemical synthesis, chemistry)
• Coumarins (chemical synthesis, chemistry)
• Fluorometry
• Humans
• Hydrolysis
• Models, Molecular
• Structure-Activity Relationship