Affiliation:
1. School of Pharmaceutical Science Shanxi Medical University Shanxi 030001 P. R. China
2. Shanxi Key Laboratory of Innovative Drug for the Treatment of Serious Diseases Basing on the Chronic Inflammation Shanxi University of Traditional Chinese Medicine Shanxi 030619 P. R. China
Abstract
AbstractMyeloid 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 in 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±0.88 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 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.
Funder
National Natural Science Foundation of China
Shanxi Province Science Foundation for Youths
Shanxi Scholarship Council of China
Subject
Molecular Biology,Molecular Medicine,General Chemistry,Biochemistry,General Medicine,Bioengineering