Soluble sugar-based quinoline derivatives as new antioxidant modulators of metal-induced amyloid aggregation

Valentina Oliveri, Giuseppa I. Grasso, Francesco Bellia, Francesco Attanasio, Maurizio Viale, Graziella Vecchio

Research output: Contribution to journalArticle

Abstract

Oxidative stress and protein aggregation have been demonstrated to be the major factors involved in neurodegenerative diseases. Metal ions play a pivotal role, acting as mediators of neurotoxicity either by favoring or redox cycling. Thus, they represent a promising and suitable therapeutic target for the treatment of neurodegenerative disorders. In particular, the development of bifunctional or multifunctional molecules, which have antiaggregant and metal-chelating/antioxidant properties, may be considered as a valuable strategy for the treatment of neurodegeneration considering its multifactorial nature. Herein, we report the design and the characterization of four new multifunctional sugar-appended 8-hydroxyquinolines focusing on the effects of the conjugation with trehalose, a nonreducing disaccharide involved in the protection of proteins and cells against environmental stresses. These glycoconjugates do not exhibit any antiproliferative activity against three human cell lines of different histological origin, unlike 8-hydroxyquinolines. The multiple properties of the new derivatives are highlighted, reporting their Cu2+ and Zn2+ binding ability, and antioxidant and antiaggregant capacities. In particular, these latter were determined by different assays, including the evaluation of their ability to modulate or even suppress the aggregation of Aβ1-40 and Aβ1-42 peptides induced by copper or zinc ions.

Original languageEnglish
Pages (from-to)2591-2602
Number of pages12
JournalInorganic Chemistry
Volume54
Issue number6
DOIs
Publication statusPublished - Mar 16 2015

Fingerprint

Oxyquinoline
quinoline
antioxidants
sugars
Amyloid
Sugars
Neurodegenerative Diseases
Modulators
modulators
Agglomeration
Antioxidants
Metals
Ions
Neurodegenerative diseases
Derivatives
proteins
Trehalose
Glycoconjugates
Oxidative stress
Cytoprotection

ASJC Scopus subject areas

  • Inorganic Chemistry
  • Physical and Theoretical Chemistry
  • Medicine(all)

Cite this

Soluble sugar-based quinoline derivatives as new antioxidant modulators of metal-induced amyloid aggregation. / Oliveri, Valentina; Grasso, Giuseppa I.; Bellia, Francesco; Attanasio, Francesco; Viale, Maurizio; Vecchio, Graziella.

In: Inorganic Chemistry, Vol. 54, No. 6, 16.03.2015, p. 2591-2602.

Research output: Contribution to journalArticle

Oliveri, Valentina ; Grasso, Giuseppa I. ; Bellia, Francesco ; Attanasio, Francesco ; Viale, Maurizio ; Vecchio, Graziella. / Soluble sugar-based quinoline derivatives as new antioxidant modulators of metal-induced amyloid aggregation. In: Inorganic Chemistry. 2015 ; Vol. 54, No. 6. pp. 2591-2602.
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