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 language | English |
|---|---|
| Pages (from-to) | 2591-2602 |
| Number of pages | 12 |
| Journal | Inorganic Chemistry |
| Volume | 54 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Mar 16 2015 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Soluble sugar-based quinoline derivatives as new antioxidant modulators of metal-induced amyloid aggregation
AU - Oliveri, Valentina
AU - Grasso, Giuseppa I.
AU - Bellia, Francesco
AU - Attanasio, Francesco
AU - Viale, Maurizio
AU - Vecchio, Graziella
PY - 2015/3/16
Y1 - 2015/3/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84924871979&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924871979&partnerID=8YFLogxK
U2 - 10.1021/ic502713f
DO - 10.1021/ic502713f
M3 - Article
C2 - 25732904
AN - SCOPUS:84924871979
VL - 54
SP - 2591
EP - 2602
JO - Inorganic Chemistry
JF - Inorganic Chemistry
SN - 0020-1669
IS - 6
ER -