Rational approach to an antiprion compound with a multiple mechanism of action. (October 2015)

• Record Type: Journal Article
• Authors: Bolognesi, Maria Laura; Bongarzone, Salvatore; Aulic, Suzana; Ai Tran, Hoang Ngoc; Prati, Federica; Carloni, Paolo; Legname, Giuseppe
• Is Part Of: Future medicinal chemistry. Volume 7:Number 16(2015)
• Page Start: 2113
• Page End: 2120
• Publication Date: 2015-10
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc.15.79
• Languages: English
• ISSNs: 1756-8919

Abstract

Background: The main pathogenic event of prion disorders has been identified in the deposition of the disease-associated prion protein (PrP Sc ), which is accompanied by metal dyshomeostasis.Results: The multitarget-directed ligand1, designed by combining a heteroaromatic prion recognition motif to an 8-hydroxyquinoline metal chelator, has been developed as a potential antiprion disease-modifying agent. Importantly, 1 was found to effectively clear PrP Sc from scrapie-infected cells, and, at the same time, inhibit metal-induced prion aggregation and reactive oxygen species generation.1 was also characterized in terms of pharmacokinetic properties in a preliminary in vitro investigation.Conclusion: Compound1 has emerged as a suitable lead candidate against prion diseases and as a good starting point for a further optimization process.