Synthesis and Biological Evaluation of Naproxen Derivatives as Novel NLRP3 Inhibitors

• Material Type: 記事
• Title: Synthesis and Biological Evaluation of Naproxen Derivatives as Novel NLRP3 Inhibitors
• Author Heading: Li Yonglian; Wong Vincent Kam Wai; You Zonglin; Chen Min; Zhang Kun; Liu Wenfeng; Zhao Suqing
• Publication Date: 2024-11-21
• Publication Date (W3CDTF): 2024-11-21
• Periodical title: Ｃｈｅｍ． Ｐｈａｒｍ． Ｂｕｌｌ．
• No. or year of volume/issue: 72 11
• Volume: 72
• Issue: 11
• Pages: 979-988
• Publication date of volume/issue (W3CDTF): 2024-11-21
• ISSN (Periodical Title): 00092363
• Publication (Periodical Title): The Pharmaceutical Society of Japan
• Text Language Code: en
• Subject Heading: naproxen derivative; cinnamic acid; pro-inflammatory cytokine; pyrin domain containing protein 3
• Target Audience: 一般
• Standard No. (Other): PMID : 39566971
• DOI: 10.1248/cpb.c24-00465; https://doi.org/10.1248/cpb.c24-00465
• Related Material (URI): https://www.jstage.jst.go.jp/article/cpb/72/11/72_c24-00465/_pdf; https://search.jamas.or.jp/link/ui/2025314444
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• Data Provider (Database): 国立情報学研究所 : CiNii Research; https://cir.nii.ac.jp/
• Original Data Provider (Database): Japan Link Center; https://japanlinkcenter.org/top; Crossref; https://www.crossref.org; PubMed; https://pubmed.ncbi.nlm.nih.gov

• Summary, etc.: <p>Naproxen, widely used to treat anti-inflammatory diseases, would cause serious of side effects. Based on the biological activities of cinnamic acid, naproxen derivatives containing cinnamic acid were designed, synthesized and used to enhance their anti-inflammatory activities and safeties. The results investigated that thirty novel naproxen derivatives had inhibitory effects on the nitric oxide (NO) release in RAW264.7 macrophage cells. A majority of naproxen derivatives showed the lower degree of cytotoxicity than that of naproxen. <i>In vitro</i> studies revealed that <b>A22</b> (IC₅₀ = 7.38 ± 1.96 µM) blocked the activation of nuclear transcription factor κB (NF-κB) signaling pathway and pyrin domain containing protein 3 (NLRP-3) inflammasome in a concentration dependent manner, thereby down-regulating the expression of pro-inflammatory cytokines, such as interleukin (IL)-1β, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Docking studies confirmed that <b>A22</b> exhibited a well-fitting into the NLRP3 active site. Accordingly, <b>A22</b> might be a novel NLRP3 inhibitor to treat inflammatory diseases.</p>
• DOI: 10.1248/cpb.c24-00465
• Access Restrictions: インターネット公開
• Data Provider (Database): 科学技術振興機構 : J-STAGE; http://www.jstage.jst.go.jp