Structure-activity relationship study of 9-aminoacridine compounds in scrapie-infected neuroblastoma cells

  • Bioorg Med Chem Lett. 2006 Sep 15;16(18):4913-6. doi: 10.1016/j.bmcl.2006.06.050.
Barnaby C H May  1 ,  Juanita Witkop ,  John Sherrill ,  Marc O Anderson ,  Peter B Madrid ,  Julie A Zorn ,  Stanley B Prusiner ,  Fred E Cohen ,  R Kiplin Guy
Affiliations
  • 1. Institute for Neurodegenerative Diseases, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143, USA. [email protected]
PMID: 16860557 DOI: 10.1016/j.bmcl.2006.06.050
Abstract

A focused library of variously substituted 9-aminoacridine compounds was screened for bioactivity against accumulation of the infectious Prion Protein isoform, denoted PrP(Sc), in a cell model of prion replication. The efficacy of compounds against PrP(Sc) accumulation was influenced by both substituents of the distal tertiary amine and acridine heterocycle, while cellular cytotoxicity was encoded in the acridine heterocycle substituents.