Carnoquinolines Target Copper Dyshomeostasis, Aberrant Protein‐Protein Interactions, and Oxidative Stress

Metal dysregulation, oxidative stress, protein modification, and aggregation are factors strictly interrelated and associated with neurodegenerative pathologies. As such, all 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. Here, we report the synthesis and in-depth analysis of the first hybrids of carnosine and 8-hydroxyquinoline, Carnoquinolines (CarHQs), that combine the properties of the dipeptide with those of 8-hydroxyquinoline. CarHQs and their copper complexes were characterized through several techniques such as ESI-MS, NMR, UV-vis, and CD 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.