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

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
• paeonol derivatives
• design
• synthesis
• anti-inflammatory

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

This work was supported by the National Natural Science Funding of China [21977001], National College Students’ innovation and entrepreneurship training program [202010366047], Pharmaceutical innovative fund [YXCX202102].