Synthesis and Anti-Inflammatory Activity Evaluation of Benzoxazole Derivatives as New Myeloid Differentiation Protein 2 Inhibitors.
Chem Biodivers
; 20(6): e202201145, 2023 Jun.
Article
en En
| MEDLINE
| ID: mdl-37080925
ABSTRACT
Myeloid differentiation protein 2 (MD2), a key TLR4 adaptor protein for sensing LPS, plays an important role in inflammatory process and has been identified as a promising target for the treatment of a variety of inflammatory diseases. In our study, a series of benzoxazolone derivatives were synthesized, characterized and tested for anti-inflammatory activity inâ
vitro. The compounds 3c, 3d and 3g demonstrated the greatest anti-inflammatory activity against IL-6 with IC50 values of 10.14±0.08, 5.43±0.51 and 5.09±0.88â
µM, respectively. Furthermore, the bis-ANS displacement assay revealed that these compounds competitively inhibited the binding between the probe bis-ANS and the MD2 protein. The most active compound 3g, revealed a directly bind with MD2 protein via Arg90 binding and a dissociation constant value of 1.52×10-6 â
mol L-1 as determined by the biological layer interference (BLI) assay. Our finding suggested that compounds 3g could be a promising lead compound as MD2 inhibitor for further anti-inflammatory agent development.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Benzoxazoles
/
Antiinflamatorios
Tipo de estudio:
Prognostic_studies
Idioma:
En
Año:
2023
Tipo del documento:
Article