Exploitation of the nitro- and/or 4-Trifluoromethyl-decorated phenyl fragment to develop small inhibitors of Alpha-Syn fibril aggregation.
Bioorg Med Chem Lett
; 111: 129905, 2024 Oct 01.
Article
en En
| MEDLINE
| ID: mdl-39067714
ABSTRACT
Here, we report new 2-nitro and/or 4-trifluoromethylphenyl-based small molecules developed as inhibitors of alpha-Syn fibril formation. The set of eighteen compounds was inspired by well-known alpha-Syn aggregation modulators retrieved from literature. The preliminary biochemical data suggested that the two molecules out of eighteen compounds exerted activity comparable to that of reference compound SynuClean-D (SC-D, 5-nitro-6-(3-nitrophenyl)-2-oxo-4-(trifluoromethyl)-1H-pyridine-3-carbonitrile), according to Thioflavin T kinetics. Pharmacophore modelling deciphered the main structural requirements for alpha-Syn aggregation modulators. Moreover, docking and molecular dynamics simulations depicted the binding mode with the targeted alpha-Syn fibrils. The structural data of these new potential α-Syn binders might furnish additional information for understanding the mechanism of action of the ligands that specifically target the NAC domain as theranostic agents for α-synucleopathies.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Nitrocompuestos
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia