Investigation of copper binding competition between a potential anti-Alzheimer's drug and Aβ(1–16) based on voltametric and chemometric analysis

Decades of extensive research have proved that β-amyloid (Aβ) peptides and their aggregation, inducing oxidative stress in the brain, play a key role in Alzheimer’s disease (AD) development. Moreover, Aβ peptides bind to Cu(II) ions, and the resulting complexes accelerate the aggregation process while promoting the production of Reactive Oxygen Species (ROS). Recently, specific chelators capable of extracting Cu(II) from their complexes with Aβ peptides, such as bis-8-aminoquinoline derivatives, named TDMQ, have gained increasing attention. This work presents a study on a potential new drug, TDMQ20, against AD. The competition for Cu(II) ions between Aβ(1-16) and TDMQ20 was investigated using voltammetry combined with chemometric tools. Principal component analysis (PCA) results indicated that a potential anti-AD drug complexes Cu(II) in the presence of Aβ(1-16). Moreover, Multivariate curve resolution-alternating least squares (MCR-ALS) provided the individual contributions of the constituents in the investigated samples, which confirm the capability of TDMQ20 to completely extract Cu(II) ions from the Aβ(1-16)-Cu(II) complex, forming the TDMQ20-Cu(II) complex. In this manuscript, we demonstrate that electrochemical techniques combined with chemometric analysis are an effective method for testing potential drugs that chelate Cu(II) ions, which are of interest in treating neurological diseases such as Alzheimer's, Huntington's, and Wilson's disease. Moreover, a potential therapeutic activity of the anti-Alzheimer's drug is also demonstrated.