Ru(II)-arene azole complexes as anti-amyloid-ß agents.
Dalton Trans
; 2024 Aug 02.
Article
em En
| MEDLINE
| ID: mdl-39093049
ABSTRACT
With the recent clinical success of anti-amyloid-ß (Aß) monoclonal antibodies, there is a renewed interest in agents which target the Aß peptide of Alzheimer's disease (AD). Metal complexes are particularly well-suited for this development, given their structural versatility and ability to form stabile interactions with soluble Aß. In this report, a small series of ruthenium-arene complexes were evaluated for their respective ability to modulate both the aggregation and cytotoxicity of Aß. First, the stability of the complexes was evaluated in a variety of aqueous media where the complexes demonstrated exceptional stability. Next, the ability to coordinate and modulate the Aß peptide was evaluated using several spectroscopic methods, including thioflavin T (ThT) fluorescence, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Overall, the complex RuBO consistently gave the greatest inhibitory action towards Aß aggregation, which correlated with its ability to coordinate to Aß in solution. Furthermore, RuBO also had the lowest affinity for serum albumin, which is a key consideration for a neurotherapeutic, as this protein does not cross the blood brain barrier. Lastly, RuBO also displayed promising neuroprotective properties, as it had the greatest inhibition of Aß-inducted cytotoxicity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Dalton Trans
Assunto da revista:
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Reino Unido