Synthesis and Biological Evaluation of Fangchinoline Derivatives as Anti-Inflammatory Agents through Inactivation of Inflammasome.
Molecules
; 24(6)2019 Mar 23.
Article
em En
| MEDLINE
| ID: mdl-30909541
ABSTRACT
Twenty eight 7-substitued fangchinoline analogues, of which twenty two were novel, were synthesized and evaluated for their effect to inhibit lipopolysaccharide/nigericin (LPS/NIG)-induced IL-1ß release at both cell and protein levels at the concentration of 5 µM. Among them, compound 6 exhibited promising inhibitory potency against IL-ß activation with an IC50 value of 3.7 µM. Preliminary mechanism study revealed that 6 might target NLRP3 protein, and then block ASC pyroptosome formation with-NLRP3, rather than acting on the activation of the NLRP3 inflammasome (NF-κB and MAPK pathways) or caspase-1 protein. Our current study supported the potential role of compound 6 against IL-ß activation, and provided powerful information for developing fangchinoline derivatives into a novel class of anti-inflammatory agents.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzilisoquinolinas
/
Inflamassomos
/
Inflamação
/
Anti-Inflamatórios
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article