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

J Med Chem. 2003 Jun 5;46(12):2279-82. doi: 10.1021/jm0340602.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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