A Glutathione Derivative with Chelating and in vitro Neuroprotective Activities: Synthesis, Physicochemical Properties, and Biological Evaluation. Issue 11 (17th September 2013)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: ChemMedChem. Volume 8:Issue 11(2013:Nov.)
• Page Start: 1818
• Page End: 1829
• Publication Date: 2013-09-17
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201300295
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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 H₂O₂‐ 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.</p> </abstract>