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 Abeta-peptides and the 2-methoxy-6-nitro compound 7f for PrP.
Csuk
René
R
Martin-Luther-Universität Halle-Wittenberg, Organische Chemie, Halle (Saale), Germany. rene.csuk@chemie.uni-halle.de
Barthel
Alexander
A
Raschke
Christian
C
Kluge
Ralph
R
Ströhl
Dieter
D
Trieschmann
Lothar
L
Böhm
Gerald
G
D000166:Acridines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use*; D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000187:drug effects; D019281:Dimerization; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D015394:Molecular Structure; D017096:Prion Diseases / Q000188:drug therapy*; D011328:Prions / Q000187:drug effects
D000166:Acridines; D016229:Amyloid beta-Peptides; D011328:Prions