Insights into molecular mechanisms of metallodrugs using metallomic studies

La Manna, Sara; Marasco, Daniela

doi:10.1016/j.ica.2023.121816

Cited by 4 publications

(2 citation statements)

References 184 publications

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“…5−11 In this regard, recent studies about the use of metal complexes as antiaggregation agents have gained attention. 12 This is because transition metal ions such as the ions Fe 2+/3+ , Cu +/2+ , and Zn 2+ play crucial roles in brain functions and can bind Aβ peptides under physiological conditions influencing their aggregation patterns. 13−15 For example, the binding of Zn 2+ can both inhibit or promote Aβ aggregation, depending on the concentration of Zn ions and other factors.…”

Section: ■ Introductionmentioning

confidence: 99%

“…One of the most extensively studied events that leads to AD is the harmful accumulation of Aβ peptides . Consequently, research is focused on the design of small molecules as potential chemical agents to prevent Aβ aggregation. − In this regard, recent studies about the use of metal complexes as antiaggregation agents have gained attention . This is because transition metal ions such as the ions Fe 2+/3+ , Cu +/2+ , and Zn 2+ play crucial roles in brain functions and can bind Aβ peptides under physiological conditions influencing their aggregation patterns. − For example, the binding of Zn 2+ can both inhibit or promote Aβ aggregation, depending on the concentration of Zn ions and other factors .…”

Section: Introductionmentioning

confidence: 99%

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Comparative Analysis of the Inhibitory Mechanism of Aβ_1–42 Aggregation by Diruthenium Complexes

La Manna,

Panzetta,

Di Natale

et al. 2024

Inorg. Chem.

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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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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of the Inhibitory Mechanism of Aβ_1–42 Aggregation by Diruthenium Complexes

La Manna,

Panzetta,

Di Natale

et al. 2024

Inorg. Chem.

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Exploring metalloproteins found in the secretion of venomous species: Biological role and therapeutical applications

Lopes Júnior,

Mendes,

Sousa

et al. 2024

Advances in Protein Chemistry and Structural Biology

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Structural and theoretical exploration of an innovative unsymmetrical oxovanadium complex: Electrochemical analysis and in vitro antibacterial screening

Boucekine,

Ouari,

Merzougui

et al. 2024

Journal of Molecular Structure

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Insights into molecular mechanisms of metallodrugs using metallomic studies

Cited by 4 publications

References 184 publications

Comparative Analysis of the Inhibitory Mechanism of Aβ_1–42 Aggregation by Diruthenium Complexes

Comparative Analysis of the Inhibitory Mechanism of Aβ_1–42 Aggregation by Diruthenium Complexes

Exploring metalloproteins found in the secretion of venomous species: Biological role and therapeutical applications

Structural and theoretical exploration of an innovative unsymmetrical oxovanadium complex: Electrochemical analysis and in vitro antibacterial screening

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Insights into molecular mechanisms of metallodrugs using metallomic studies

Cited by 4 publications

References 184 publications

Comparative Analysis of the Inhibitory Mechanism of Aβ1–42 Aggregation by Diruthenium Complexes

Comparative Analysis of the Inhibitory Mechanism of Aβ1–42 Aggregation by Diruthenium Complexes

Exploring metalloproteins found in the secretion of venomous species: Biological role and therapeutical applications

Structural and theoretical exploration of an innovative unsymmetrical oxovanadium complex: Electrochemical analysis and in vitro antibacterial screening

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Product

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Comparative Analysis of the Inhibitory Mechanism of Aβ_1–42 Aggregation by Diruthenium Complexes

Comparative Analysis of the Inhibitory Mechanism of Aβ_1–42 Aggregation by Diruthenium Complexes