Propidium-based polyamine ligands as potent inhibitors of acetylcholinesterase and acetylcholinesterase-induced amyloid-beta aggregation

J Med Chem. 2005 Jan 13;48(1):24-7. doi: 10.1021/jm049156q.

Abstract

Heterodimers 4 and 5 were effective inhibitors of acetylcholinesterase (AChE) activity and AChE-induced amyloid-beta (A beta) aggregation. The peculiar biological profile of 4 can be relevant in studying the molecular basis underlying the nonclassical action of AChE and in addressing the question whether AChE inhibitors can affect the neurotoxic cascade leading to Alzheimer's disease. Compound 4 emerged as the most potent heterodimer so far available to inhibit AChE-induced A beta aggregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / drug effects
  • Acetylcholinesterase / metabolism*
  • Amyloid beta-Peptides / drug effects
  • Amyloid beta-Peptides / metabolism*
  • Biochemistry / methods
  • Cholinesterase Inhibitors / chemistry*
  • Cholinesterase Inhibitors / metabolism
  • Cholinesterase Inhibitors / pharmacology*
  • Dimerization
  • Drug Design
  • Drug Evaluation, Preclinical / methods
  • Fluorometry / methods
  • Humans
  • Hydrolysis
  • Inhibitory Concentration 50
  • Ligands
  • Polyamines / chemistry*
  • Propidium / chemistry*
  • Structure-Activity Relationship

Substances

  • Amyloid beta-Peptides
  • Cholinesterase Inhibitors
  • Ligands
  • Polyamines
  • Propidium
  • Acetylcholinesterase