A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease

Abstract

Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a Mn^II -based superoxide dismutase (SOD) mimic ([Mn^II (L)]⁺ , 1⁺ ) as a pro-drug candidate to target Cu^II -associated events, namely, Cu^II -induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1⁺ is able to remove Cu^II from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1⁺ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity.

Keywords: Alzheimer′s disease; antioxidants; drug development; enzyme mimics; metal complexes; pro-drugs.