Benzofuran-based hybrid compounds for the inhibition of cholinesterase activity, beta amyloid aggregation, and abeta neurotoxicity

J Med Chem. 2008 May 22;51(10):2883-6. doi: 10.1021/jm8002747. Epub 2008 Apr 18.

Abstract

The complex etiology of Alzheimer's disease (AD) prompts scientists to develop multitarget strategies to combat causes and symptoms. We therefore designed, synthesized, and tested new hybrid molecules linking a benzofuran ring to a N-methyl- N-benzylamine through a heptyloxy chain, affording a series of potential multifunctional drugs for AD. The cholinesterase inhibitory activity was extended to the inhibition of Abeta fibril formation for 1, 3, and 5. Compound 3 showed an additional neuroprotective effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / chemistry
  • Amyloid / chemistry
  • Amyloid / metabolism
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism
  • Benzofurans / chemical synthesis*
  • Benzofurans / chemistry
  • Benzofurans / pharmacology
  • Butyrylcholinesterase / chemistry
  • Cell Line
  • Cell Survival / drug effects
  • Cholinesterase Inhibitors / chemical synthesis*
  • Cholinesterase Inhibitors / chemistry
  • Cholinesterase Inhibitors / pharmacology
  • Humans
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Peptide Fragments / chemistry*
  • Peptide Fragments / metabolism
  • Structure-Activity Relationship

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Benzofurans
  • Cholinesterase Inhibitors
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • Acetylcholinesterase
  • Butyrylcholinesterase