Design, synthesis and bioactivity evaluation of fisetin derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury

  • Bioorg Med Chem. 2021 Nov 1;49:116456. doi: 10.1016/j.bmc.2021.116456.
Xiemin Wang  1 ,  Jun Yang  1 ,  Bingyu Ding  2 ,  Pan Chen  1 ,  Zhengwei Xu  2 ,  Yunxi Zhao  2 ,  Pengqin Chen  1 ,  Nipon Chattipakorn  3 ,  Guang Liang  4 ,  Di Wu  5 ,  Qidong Tang  6
Affiliations
  • 1. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China.
  • 2. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
  • 3. Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
  • 4. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou, Zhejiang 325001, China; School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang 311399, China. Electronic address: [email protected].
  • 5. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: [email protected].
  • 6. Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China. Electronic address: [email protected].
PMID: 34628233 DOI: 10.1016/j.bmc.2021.116456
Abstract

Acute lung injury (ALI) refers to a common and life-threatening disease attributed to inflammation. However, effective drug treatments have been rare for ALI. Natural products have been considered as a vital source of drug discovery which indicates that it's a workable method to find new anti-inflammatory drugs in natural products. Inspired by the various biological activities of fisetin, we reported the design and synthesis of a series of fisetin derivatives which were also evaluated for their anti-inflammatory activities in J774A.1 macrophages. Most of the obtain derivatives could effectively inhibit the release of IL-6 and TNF-α in vitro experiments without cytotoxicity. The most promising compound 5b exhibited significant in vivo anti-inflammatory activity in the model of LPS-induced ALI in mice. On the whole, this study could provide novel candidates for the treatment of ALI.

Keywords
Acute lung injury; Anti-inflammatory; Fisetin derivatives; Natural product.
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