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Carnoquinolines Target Copper Dyshomeostasis, Aberrant Protein–Protein Interactions, and Oxidative Stress
Author(s) -
Bellia Francesco,
Grasso Giuseppa Ida,
Ahmed Ikhlas Mohamed Mohamud,
Oliveri Valentina,
Vecchio Graziella
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202001591
Subject(s) - oxidative stress , neurodegeneration , carnosine , chemistry , dipeptide , antioxidant , circular dichroism , protein aggregation , copper , reactive oxygen species , amyloid (mycology) , biochemistry , radical , imidazole , biophysics , ceruloplasmin , stereochemistry , peptide , organic chemistry , biology , medicine , inorganic chemistry , disease
Metal dysregulation, oxidative stress, protein modification, and aggregation are factors strictly interrelated and associated with neurodegenerative pathologies. As such, all of these aspects represent valid targets to counteract neurodegeneration and, therefore, the development of metal‐binding compounds with other properties to combat multifactorial disorders is definitely on the rise. Herein, the synthesis and in‐depth analysis of the first hybrids of carnosine and 8‐hydroxyquinoline, carnoquinolines (CarHQs), which combine the properties of the dipeptide with those of 8‐hydroxyquinoline, are reported. CarHQs and their copper complexes were characterized through several techniques, such as ESI‐MS and NMR, UV/Vis, and circular dichroism spectroscopy. CarHQs can modulate self‐ and copper‐induced amyloid‐β aggregation. These hybrids combine the antioxidant activity of their parent compounds. Therefore, they can simultaneously scavenge free radicals and reactive carbonyl species, thanks to the phenolic group and imidazole ring. These results indicate that CarHQs are promising multifunctional candidates for neurodegenerative disorders and they are worthy of further studies.