A Glutathione Derivative with Chelating and in vitro Neuroprotective Activities: Synthesis, Physicochemical Properties, and Biological Evaluation
| Autor: | Ivana Cacciatore, Ester Sara Di Filippo, Piera Sozio, Antonio Di Stefano, Erika Fornasari, Catia Cornacchia, Stefania Fulle, Alessio Ferrone, Francesco Pinnen, Rita La Rovere, Lisa Marinelli, Annalisa Dean, Valerio Di Marco, Antonia Patruno, Leonardo Baldassarre |
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| Rok vydání: | 2013 |
| Předmět: |
Antioxidant
tripeptide Cell Survival medicine.medical_treatment chelation therapy zinc copper iron glutathione 8-hydroxyquinoline medicine.disease_cause Biochemistry Neuroprotection Antioxidants Cell Line Neuroblastoma chemistry.chemical_compound In vivo Drug Discovery medicine Humans Chelation General Pharmacology Toxicology and Pharmaceutics Chelating Agents Pharmacology Molecular Structure Organic Chemistry Glutathione Hydrogen-Ion Concentration Oxyquinoline In vitro Neuroprotective Agents Solubility chemistry Molecular Medicine Reactive Oxygen Species Homeostasis Oxidative stress |
| Zdroj: | ChemMedChem. 8:1818-1829 |
| ISSN: | 1860-7179 |
| DOI: | 10.1002/cmdc.201300295 |
| Popis: | 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 H2 O2 - 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. |
| Databáze: | OpenAIRE |
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