Discovery of novel paeonol-based derivatives against skin inflammation in vitro and in vivo.
J Enzyme Inhib Med Chem
; 37(1): 817-831, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-35220836
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Acetofenonas
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Pele
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Anti-Inflamatórios não Esteroides
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Descoberta de Drogas
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Inflamação
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article