2. Academic Validation
  3. 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

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

  • Bioorg Med Chem Lett. 2020 Sep 1;30(17):127373. doi: 10.1016/j.bmcl.2020.127373.
Yu-Ying Zhang 1,  Qian-Qian Zhang 1,  Juan Zhang 2,  Jia-Li Song 1,  Jia-Cheng Li 1,  Ke Han 3,  Jin-Tian Huang 4,  Cheng-Shi Jiang 5,  Hua Zhang 6
Affiliations

Affiliations

  • 1 School of Biological Science and Technology, University of Jinan, Jinan 250022, China.
  • 2 School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: bio_zhangj@ujn.edu.cn.
  • 3 Department of Traumatic Orthopaedics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China.
  • 4 Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, China.
  • 5 School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: bio_jiangcs@ujn.edu.cn.
  • 6 School of Biological Science and Technology, University of Jinan, Jinan 250022, China. Electronic address: bio_zhangh@ujn.edu.cn.
PMID: 32738985 DOI: 10.1016/j.bmcl.2020.127373
Abstract

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.

Keywords

1,2,4-oxadiazole; Anti-inflammatory activity; NF-κB; NO production; Structural optimization.

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