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

Area of Science:

• Medicinal Chemistry
• Neuroscience
• Biochemistry

Background:

• Neurodegenerative diseases involve complex factors like metal dysregulation, oxidative stress, and protein aggregation.
• Developing multifunctional compounds targeting these interconnected pathways is crucial for effective treatment.

Purpose of the Study:

• To synthesize and characterize novel carnosine and 8-hydroxyquinoline hybrids, termed carnoquinolines (CarHQs).
• To evaluate the potential of CarHQs and their copper complexes as therapeutic agents for neurodegenerative disorders.

Main Methods:

• Synthesis of carnoquinolines (CarHQs).
• Characterization using ESI-MS, NMR, UV/Vis, and circular dichroism spectroscopy.
• Assessment of modulation of amyloid-β aggregation and antioxidant activities.

Main Results:

• Successfully synthesized and characterized the first carnosine-8-hydroxyquinoline hybrids (CarHQs).
• CarHQs demonstrated the ability to modulate both self- and copper-induced amyloid-β aggregation.
• These hybrids possess combined antioxidant properties, scavenging free radicals and reactive carbonyl species.

Conclusions:

• Carnoquinolines (CarHQs) are promising multifunctional agents for neurodegenerative diseases.
• Their ability to address metal dysregulation, oxidative stress, and protein aggregation warrants further investigation.