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 ligand 1, 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: Compound 1 has emerged as a suitable lead candidate against prion diseases and as a good starting point for a further optimization process.

Rational approach to an antiprion compound with a multiple mechanism of action / Bolognesi, Ml; Bongarzone, S; Aulic, S; Ai Tran, Hn; Prati, F; Carloni, P; Legname, Giuseppe. - In: FUTURE MEDICINAL CHEMISTRY. - ISSN 1756-8919. - 7:16(2015), pp. 2113-2120. [10.4155/fmc.15.79]

Rational approach to an antiprion compound with a multiple mechanism of action

Legname, Giuseppe
2015-01-01

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 ligand 1, 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: Compound 1 has emerged as a suitable lead candidate against prion diseases and as a good starting point for a further optimization process.
2015
7
16
2113
2120
https://www.future-science.com/doi/10.4155/fmc.15.79
Bolognesi, Ml; Bongarzone, S; Aulic, S; Ai Tran, Hn; Prati, F; Carloni, P; Legname, Giuseppe
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/14412
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