Synthesis of Monomeric and Dimeric Acridine Compounds as Potential Therapeutics in Alzheimer and Prion Diseases

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 A beta-peptides and the 2-methoxy-6-nitro compound 7f for PrP.