Discovery of novel chrysin derivatives as potential Anti-Psoriasis agents

[Display omitted] •Twenty novel chrysin derivatives 4a-4 t were designed and synthesized.•The anti-inflammatory activity of compounds 4a-4 t was evaluated in RAW264.7 cells, and compounds 4 h, 4 k, and 4o had higher inflammatory activities and lower toxicity than chrysin.•Compound 4o inhibited the l...

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Veröffentlicht in:Bioorganic chemistry 2024-09, Vol.150, p.107599, Article 107599
Hauptverfasser: Zhao, Xiujuan, Du, Chenghong, Zeng, Yongcheng, Chen, Yanmei, Xu, Jiacai, Yin, Xunqing, Hu, Chunyan, Mao, Zewei, Lin, Yuping
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Sprache:eng
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Zusammenfassung:[Display omitted] •Twenty novel chrysin derivatives 4a-4 t were designed and synthesized.•The anti-inflammatory activity of compounds 4a-4 t was evaluated in RAW264.7 cells, and compounds 4 h, 4 k, and 4o had higher inflammatory activities and lower toxicity than chrysin.•Compound 4o inhibited the level of inflammatory cytokines in HaCaT cells and IMQ-induced psoriasis mice, and had a good effect on treating the inflammation of psoriasis.•Compound 4o could be a novel drug for the potential treatment of psoriasis. The mechanism might be related to the NF-κB and STAT3 signaling pathways. Psoriasis is a chronic inflammatory disease and is difficult to cure. In this work, a series of novel chrysin derivatives have been designed and prepared while evaluating anti-inflammatory activities in vitro and in vivo. In vitro, RAW264.7 cells were used to detect the inflammatory activities at first, and compounds 4h, 4k, and 4o significantly decreased the levels of NO, TNF-α, and IL-6. In particular, compound 4o showed superior anti-inflammatory activities than other compounds. Moreover, compound 4o decreased the level of IL-17A in LPS-induced HaCaT cells in vitro. The effect and mechanism of anti-inflammatory activities on psoriasis were determined by imiquimod (IMQ)-induced psoriasis-like mice in vivo. Compound 4o deduced the level of IL-6, IL-17A, IL-22, IL-23, and TNF-α, and showed potent anti-psoriasis activity. Further mechanism study suggested that compound 4o could improve the skin inflammation of psoriasis by inhibiting the NF-κB and STAT3 signaling pathways.
ISSN:0045-2068
1090-2120
1090-2120
DOI:10.1016/j.bioorg.2024.107599