期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 161, 期 -, 页码 22-38出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2018.09.068
关键词
MyD88; 2-Amino-4-phenylthiazole; Macrophages; Anti-inflammation; Acute lung injury
资金
- National Key Research Project [2017YFA0506000]
- National Natural Science Foundation of China [81622043, 81770825, 81773579]
- Natural Science Funding of Zhejiang Province [LR16H310001, LY17B020008]
Myeloid differentiation primary response protein 88 (MyD88), an essential adapter protein used by toll like receptors (TLR), is a promising target molecule for the treatment of respiratory inflammatory diseases. Previous studies explored the activities of novel 2-amino-4-phenylthiazole analogue (6) in inflammation-induced cancer, and identified the analogue as an inhibitor of MyD88 toll/interleukin-1 receptor (TIR) homology domain dimerization. Here, we describe the synthesis of 47 new analogues by modifying different sites on this lead compound and assessed their anti-inflammatory activities in lipopolysaccharide-induced mouse primary peritoneal macrophages (MPMs). The most promising compound, 15d, was found to effectively interact with MyD88 protein and prevented formation of the MyD88 homodimeric complex. Furthermore, 15d showed in vivo anti-inflammatory activity in LPS-caused model of acute lung injury. This work provides new candidates as MyD88 inhibitors to combat inflammation diseases. (C) 2018 Elsevier Masson SAS. All rights reserved.
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