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A Glutathione Derivative with Chelating and in vitro Neuroprotective Activities: Synthesis, Physicochemical Properties, and Biological Evaluation
Author(s) -
Cacciatore Ivana,
Cornacchia Catia,
Fornasari Erika,
Baldassarre Leonardo,
Pinnen Francesco,
Sozio Piera,
Di Stefano Antonio,
Marinelli Lisa,
Dean Annalisa,
Fulle Stefania,
Di Filippo Ester Sara,
La Rovere Rita Maria Laura,
Patruno Antonia,
Ferrone Alessio,
Di Marco Valerio
Publication year - 2013
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201300295
Subject(s) - neuroprotection , glutathione , chelation , in vitro , oxidative stress , chemistry , in vivo , pharmacology , antioxidant , biochemistry , peptide , medicine , biology , enzyme , organic chemistry , microbiology and biotechnology
Abstract Metal‐ion dysregulation and oxidative stress have been linked to the progressive neurological decline associated with neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Herein we report the synthesis and chelating, antioxidant, and in vitro neuroprotective activities of a novel derivative of glutathione, GS(HQ)H, endowed with an 8‐hydroxyquinoline group as a metal‐chelating moiety. In vitro results showed that GS(HQ)H may be stable enough to be absorbed unmodified and arrive intact to the blood–brain barrier, that it may be able to remove Cu II and Zn II from the Aβ peptide without causing any copper or zinc depletion in vivo, and that it protects SHSY‐5Y human neuroblastoma cells against H 2 O 2 ‐ and 6‐OHDA‐induced damage. Together, these findings suggest that GS(HQ)H could be a potential neuroprotective agent for the treatment of neurodegenerative diseases in which a lack of metal homeostasis has been reported as a key factor.