2. Academic Validation
  3. Discovery of novel paeonol-based derivatives against skin inflammation in vitro and in vivo

Discovery of novel paeonol-based derivatives against skin inflammation in vitro and in vivo

  • J Enzyme Inhib Med Chem. 2022 Dec;37(1):817-831. doi: 10.1080/14756366.2022.2043852.
Jing Wu 1 2,  Ren De Zhu 1 2,  Guo Min Cao 1 2,  Jun Cheng Du 1 2,  Xin Liu 3,  Liang Zhuo Diao 1 2,  Zhao Yan Zhang 1 2,  Yang Sheng Hu 1 2 4,  Xin Hua Liu 1 2,  Jing Bo Shi 1 2
Affiliations

Affiliations

  • 1 School of Pharmacy, Anhui Medical University, Hefei, P. R. China.
  • 2 Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, P. R. China.
  • 3 Department of Clinical Medicine, Second Clinical Medical College, Anhui Medical University, Hefei, P. R. China.
  • 4 Department of Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, P. R. China.
PMID: 35220836 DOI: 10.1080/14756366.2022.2043852
Abstract

T-LAK-cell-originated protein kinase (TOPK), a novel member of the mitogen-activated protein kinase family, is considered an effective therapeutic target for skin inflammation. In this study, a series (A - D) of paeonol derivatives was designed and synthesised using a fragment growing approach, and their anti-inflammatory activities against lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 cells were tested. Among them, compound B12 yielded the best results (IC50 = 2.14 μM) with low toxicity (IC50 > 50 µM). Preliminary mechanistic studies indicated that this compound could inhibit the TOPK-p38/JNK signalling pathway and phosphorylate downstream related proteins. A murine psoriasis-like skin inflammation model was used to determine its therapeutic effect.

Keywords

T-LAK-cell-originated protein kinase; anti-inflammatory; design; paeonol derivatives; synthesis.

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