Amide derivatives of Gallic acid: Design, synthesis and evaluation of inhibitory activities against in vitro α-synuclein aggregation.
Bioorg Med Chem
; 28(15): 115596, 2020 08 01.
Article
en En
| MEDLINE
| ID: mdl-32631566
ABSTRACT
Gallic acid (GA), a natural phenolic acid, has received numerous attention because of its anti-oxidative, anti-inflammatory, and anti-cancer activity. More importantly, GA can act as an efficient inhibitor of α-Synuclein (α-Syn) aggregation at early stages. Nevertheless, some evidences suggest that GA is unlikely to cross the blood-brain barrier because of its high hydrophilicity. Hence, GA may not be considered as a promising candidate or entering brain and directly affecting the central nervous system. Accordingly, we have designed and synthesized a series of amide derivatives of GA, some of which possess appropriate lipophilicity and hydrophilicity with LogP (2.09-2.79). Meanwhile, these sheet-like conjugated compounds have good π-electron delocalization and high ability of hydrogen-bond formation. Some compounds have shown better in vitro anti-aggregation activities than GA towards α-Syn, with IC50 down to 0.98 µM. The valid modification strategy of GA is considered an efficient way to discover novel inhibitors of α-Syn aggregation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Alfa-Sinucleína
/
Multimerización de Proteína
/
Amidas
/
Ácido Gálico
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China