Arylacryl amides: Design, synthesis and the protection against cisplatin-induced acute kidney injury via TLR4/STING/NF-κB pathway.
Bioorg Chem
; 146: 107303, 2024 May.
Article
en En
| MEDLINE
| ID: mdl-38521012
ABSTRACT
Arylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK2 cells. Furthermore, 9d can interact with TLR4 to inhibit TLR4/STING/NF-κB pathway in the RAW264.7 cell. In vivo AKI mice model, 9d significantly downregulated the level of serum creatinine (Scr), blood urea nitrogen (BUN) and the inflammatory factors (IL-1ß, IL-6, TNF-α) to improve kidney function. Morphological and KIM-1 analyses showed that 9d alleviated cisplatin-induced tubular damage. In a word, 9d was a promising lead compound for preventive and therapeutic of AKI.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
FN-kappa B
/
Lesión Renal Aguda
Límite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos