Discovery of novel paeonol-based derivatives against skin inflammation in vitro and in vivo |
| |
| Authors: | Jing Wu Ren De Zhu Guo Min Cao Jun Cheng Du Xin Liu Liang Zhuo Diao Zhao Yan Zhang Yang Sheng Hu Xin Hua Liu Jing Bo Shi |
| |
| Affiliation: | aSchool of Pharmacy, Anhui Medical University, Hefei, P. R. China;bInflammation and Immune Mediated Diseases Laboratory of Anhui Province, Hefei, P. R. China;cDepartment of Clinical Medicine, Second Clinical Medical College, Anhui Medical University, Hefei, P. R. China;dDepartment of Medicine, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, P. R. China |
| |
| 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 |
|
|
