Copper and neurodegenerative disorders: potential drugs for possible successful treatment

Neurodegenerative disorders are by far the most difficult conditions to control. Wilson's and Parkinson's disease are neurodegenerative disorder associated with an excessive accumulation of copper in the organism. To control the symptoms of these two disorders, multifunctional drugs have been proposed. These multifunctional drugs can act as antioxidants and also as chelator of various metals, in particular copper. Among all the available drugs, PF-592379 [PF], D264 and M30 are of particular interest as they have been shown to be metal chelator. The main objective of this research is to theoretically analyse the antioxidant and chelating capacity of these molecules, to determine whether they can be considered multifunctional drugs. Density functional theory calculations were performed to characterize the bonds. Donor-acceptor electron powers were used to analyse the antioxidant capacity. In order to describe non-covalent interactions of copper complexes, the analysis of bond critical points of the electron density within the Quantum Theory of Atoms in Molecules framework and the Non-covalent Index were used. According to the results presented here, PF, D264 and M30 are drugs able to scavenge Cu and to act as antioxidants. Neurodegenerative disorders remain very mysterious and very complex. With information such as that reported here, it is possible to advance in reducing the mystery and thus contribute to find drugs able to control the symptoms of neurodegenerative disorders.