Synthesis and evaluation of 1,2,4-oxadiazole derivatives as potential anti-inflammatory agents by inhibiting NF-κB signaling pathway in LPS-stimulated RAW 264.7 cells

• Published in: Bioorganic & medicinal chemistry letters Vol. 30; no. 17; p. 127373
• Main Authors: Zhang, Yu-Ying, Zhang, Qian-Qian, Zhang, Juan, Song, Jia-Li, Li, Jia-Cheng, Han, Ke, Huang, Jin-Tian, Jiang, Cheng-Shi, Zhang, Hua
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2020
• Subjects: 1,2,4-oxadiazole; Anti-inflammatory activity; NF-κB; NO production; Structural optimization; NF-κB; Anti-inflammatory activity; NO production; 1,2,4-oxadiazole; Structural optimization
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2020.127373

[Display omitted] In this study, a series of compounds with 1,2,4-oxadiazole core was designed and synthesized for the optimization of JC01, an anti-inflammatory hit identified from our in-house compound library using NF-κB pathway luciferase assay and NO production assay. All the synthetic compounds 1–29 have been screened for their anti-inflammatory effects by evaluating their inhibition against LPS-induced NO release, and compound 17 exhibited the highest activity. Western blotting and immunofluorescence analysis revealed that 17 prominently inhibited LPS-induced activation of NF-κB in RAW264.7 cells and blocked the phosphorylation of p65. Consistent with these results, it was found that 17 prevented the nuclear translocation of NF-κB induced by LPS. These data highlighted 17 as a promising anti-inflammatory agent by inhibiting NF-κB activity.