Discovery of dronedarone and its analogues as NLRP3 inflammasome inhibitors with potent anti-inflammation activity.
Bioorg Med Chem Lett
; 46: 128160, 2021 08 15.
Article
em En
| MEDLINE
| ID: mdl-34062252
ABSTRACT
Inhibiting NLRP3 inflammasome activation is a prospective therapeutic strategy for uncontrolled inflammatory diseases. It is the first time that dronedarone, a multiply ion channel blocker, was identified as a NLRP3-inflammasome inhibitor with an IC50 value of 6.84 µM against IL-1ß release. A series of novel 5-amide benzofuran derivatives were designed and synthesized as NLRP3-inflammasome inhibitors. Compound 8c showed slightly increased activity (IC50 = 3.85 µM) against IL-1ß release. Notably, treatment with 8c could significantly inhibit NLRP3-mediated IL-1ß release and ameliorate peritoneal inflammation in a mouse model of sepsis. Collectively, 8c is a promising lead compound for further chemical development as a NLRP3 inhibitor with anti-inflammation effects.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
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Descoberta de Drogas
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Inflamassomos
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Proteína 3 que Contém Domínio de Pirina da Família NLR
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Dronedarona
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article