A metallo pro-drug to target Cu(II) in the context of Alzheimer's disease

Amandine Conte-Daban (1, 2, 3) , Vinita Ambike (4) , Régis Guillot (4) , Nicolas Delsuc (5, 6) , Clotilde Policar (5, 6) , Christelle Hureau (1, 2, 3)

1 LCC - Laboratoire de chimie de coordination
2 Toulouse INP - Institut National Polytechnique (Toulouse)
3 UT3 - Université Toulouse III - Paul Sabatier
4 LCI - Laboratoire de chimie inorganique
5 UPMC - Université Pierre et Marie Curie - Paris 6
6 LBM UMR 7203 - Laboratoire des biomolécules

Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a Mn(II)-based superoxide dismutase mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target Cu(II) associated events, i.e. Cu(II)-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-beta (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.

Mots clés: Alzheimer′s disease; Antioxidants; Drug development; Enzyme mimics; Metal complexes; Pro-drugs

Domaines: Chimie de coordination; Chimie thérapeutique

Amandine Conte-Daban, Vinita Ambike, Régis Guillot, Nicolas Delsuc, Clotilde Policar, et al.. A metallo pro-drug to target Cu(II) in the context of Alzheimer's disease. Chemistry - A European Journal, 2018, 24 (20), pp.5095-5099. ⟨10.1002/chem.201706049⟩. ⟨hal-01685637⟩