Synthesis of monomeric and dimeric acridine compounds as potential therapeutics in Alzheimer and prion diseases

Arch Pharm (Weinheim). 2009 Dec;342(12):699-709. doi: 10.1002/ardp.200900065.

Abstract

Starting from substituted 9-chloroacridines, a series of quinacrine and spacered dimeric acridine compounds was prepared. Their ability to interrupt the protein association of prion- and Alzheimer-specific proteins and Ab peptides was explored using a fast screening system based on FACS analysis. The bis-acridines displayed a higher activity than the corresponding monomers. Among these derivatives, best results were obtained with the 2,4-dimethoxy-6-nitro compound 7h for Abeta-peptides and the 2-methoxy-6-nitro compound 7f for PrP.

MeSH terms

  • Acridines / chemical synthesis*
  • Acridines / pharmacology
  • Acridines / therapeutic use*
  • Alzheimer Disease / drug therapy*
  • Amyloid beta-Peptides / drug effects
  • Dimerization
  • Drug Evaluation, Preclinical / methods
  • Humans
  • In Vitro Techniques
  • Molecular Structure
  • Prion Diseases / drug therapy*
  • Prions / drug effects

Substances

  • Acridines
  • Amyloid beta-Peptides
  • Prions