Design, synthesis and anti-inflammatory activity study of lansiumamide analogues for treatment of acute lung injury.
Biomed Pharmacother
; 166: 115412, 2023 Oct.
Article
en En
| MEDLINE
| ID: mdl-37660652
ABSTRACT
Acute lung injury (ALI) is an inflammation-mediated respiratory disease with a high mortality rate. Medications with anti-inflammatory small molecules have been demonstrated in phase I and II clinical trials to considerably reduce the ALI mortality. In this study, two series of lansiumamide analogues were designed, synthesized, and evaluated for anti-inflammatory activity for ALI treatment. We found that compound 8n exhibited the best anti-inflammatory activity through inhibiting LPS-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) in Raw264.7 cells and activating the Nrf2/HO-1 pathway. Furthermore, we discovered in a LPS-induced ALI mice model that compound 8n significantly reduced the infiltration of inflammatory cells into lung tissue to achieve the effect of protecting lung tissues and improving ALI. Additionally, our mice model study revealed that compound 8n had a good expectorant effect. These results consistently support that lansiumamide analogue 8n represents a new class of anti-inflammatory agents with potential as a lead compound for further development into a therapeutic drug for ALI treatment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Lipopolisacáridos
/
Lesión Pulmonar Aguda
Límite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2023
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
FR
/
FRANCE
/
FRANCIA
/
FRANÇA