Discovery of novel paeonol-based derivatives against skin inflammation in vitro and in vivo
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 ( ) of paeonol derivatives was designed and synthesised using a fragment growing approach, and thei...
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Veröffentlicht in: | Journal of enzyme inhibition and medicinal chemistry 2022-12, Vol.37 (1), p.817-831 |
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Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
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Zusammenfassung: | 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 (
) 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
yielded the best results (IC
= 2.14 μM) with low toxicity (IC
> 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. |
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ISSN: | 1475-6366 1475-6374 |
DOI: | 10.1080/14756366.2022.2043852 |