Comparative Analysis of the Inhibitory Mechanism of Aβ<sub>1–42</sub> Aggregation by Diruthenium Complexes

  1. La Manna, Sara 6
  2. Panzetta, Valeria 34
  3. Di Natale, Concetta 3
  4. Cipollone, Irene 12
  5. Monti, Maria 12
  6. Netti, Paolo A. 34
  7. Terán, Aarón 57
  8. Sánchez-Peláez, Ana E. 5
  9. Herrero, Santiago 5
  10. Merlino, Antonello 1
  11. Marasco, Daniela 6
  1. 1 Department of Chemical Sciences, University of Naples “Federico II”, Naples 80126, Italy
  2. 2 CEINGE Biotecnologie Avanzate “Franco Salvatore” S.c.a r.l., Naples 80131, Italy
  3. 3 Department of Chemical, Materials, and Industrial Production Engineering (DICMaPI), University of Naples Federico II, Naples 80125, Italy
  4. 4 Interdisciplinary Research Centre on Biomaterials (CRIB), University of Naples Federico II, Istituto Italiano di Tecnologia, Naples 80125, Italy
  5. 5 MatMoPol Research Group, Department of Inorganic Chemistry, Faculty of Chemical Science, Complutense University of Madrid, Avenida Complutense s/n, Madrid 28040, Spain
  6. 6 Department of Pharmacy, University of Naples “Federico II”, Naples 80131, Italy
  7. 7 MUSICHEM Research Group, Department of Physics “E. Pancini”, University of Naples Federico II, Complesso Universitario di Monte Sant’Angelo, Via Cinthia, 21, Naples 80126, Italy
Erakutsi afiliazioak +
Aldizkaria:
Inorganic Chemistry

ISSN: 0020-1669,  1520-510X

Argitalpen urtea: 2024

Mota: Artikulua

DOI: 10.1021/ACS.INORGCHEM.4C01218 GOOGLE SCHOLAR lock_openSarbide irekia editor

Beste argitalpen batzuk: Inorganic Chemistry

Laburpena

There is a growing interest in the search for metal-based therapeutics for protein misfolding disorders such as Alzheimer’s disease (AD). A novel and largely unexplored class of metallodrugs is constituted by paddlewheel diruthenium complexes, which exhibit unusual water solubility and stability and unique coordination modes to proteins. Here, we investigate the ability of the complexes [Ru2Cl(DPhF)(O2CCH3)3]·H2O (1), [Ru2Cl(DPhF)2(O2CCH3)2]·H2O (2), and K2[Ru2(DPhF)(CO3)3]·3H2O (3) (DPhF– = N,N′-diphenylformamidinate) to interfere with the amyloid aggregation of the Aβ1–42 peptide. These compounds differ in charge and steric hindrance due to the coordination of a different number of bulky ligands. The mechanisms of action of the three complexes were studied by employing a plethora of physicochemical and biophysical techniques as well as cellular assays. All these studies converge on different mechanisms of inhibition of amyloid fibrillation: complexes 1 and 2 show a clear inhibitory effect due to an exchange ligand process in the Ru2 unit aided by aromatic interactions. Complex 3 shows no inhibition of aggregation, probably due to its negative charge in solution. This study demonstrates that slight variations in the ligands surrounding the bimetallic core can modulate the amyloid aggregation inhibition and supports the use of paddlewheel diruthenium complexes as promising therapeutics for Alzheimer’s disease.

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