RT Journal Article
T1 Comparative Analysis of the Inhibitory Mechanism of Aβ1–42 Aggregation by Diruthenium Complexes
A1 La Manna, Sara
A1 Panzetta, Valeria
A1 Di Natale, Concetta
A1 Cipollone, Irene
A1 Monti, Maria
A1 Netti, Paolo A.
A1 Terán More, Aaron
A1 Sánchez Peláez, Ana Edilia
A1 Herrero Domínguez, Santiago
A1 Merlino, Antonello
A1 Marasco, Daniela
AB 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.
PB American Chemical Society
YR 2024
FD 2024-05-14
LK https://hdl.handle.net/20.500.14352/113701
UL https://hdl.handle.net/20.500.14352/113701
LA eng
NO La Manna S, Panzetta V, Di Natale C, Cipollone I, Monti M, Netti PA, Terán A, Sánchez-Peláez AE, Herrero S, Merlino A, Marasco D. Comparative Analysis of the Inhibitory Mechanism of Aβ1-42 Aggregation by Diruthenium Complexes. Inorg Chem. 2024 May 27;63(21):10001-10010. doi: 10.1021/acs.inorgchem.4c01218. Epub 2024 May 14. PMID: 38742626.
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 7 abr 2025