Synthesis and Biological Evaluation of Naproxen Derivatives as Novel NLRP3 Inhibitors

• 資料種別: 記事
• タイトル: Synthesis and Biological Evaluation of Naproxen Derivatives as Novel NLRP3 Inhibitors
• 著者標目: Li Yonglian; Wong Vincent Kam Wai; You Zonglin; Chen Min; Zhang Kun; Liu Wenfeng; Zhao Suqing
• 出版年月日等: 2024-11-21
• 出版年（W3CDTF）: 2024-11-21
• タイトル（掲載誌）: Ｃｈｅｍ． Ｐｈａｒｍ． Ｂｕｌｌ．
• 巻号年月日等（掲載誌）: 72 11
• 掲載巻: 72
• 掲載号: 11
• 掲載ページ: 979-988
• 掲載年月日（W3CDTF）: 2024-11-21
• ISSN（掲載誌）: 00092363
• 出版事項（掲載誌）: The Pharmaceutical Society of Japan
• 本文の言語コード: en
• 件名標目: naproxen derivative; cinnamic acid; pro-inflammatory cytokine; pyrin domain containing protein 3
• 対象利用者: 一般
• 標準番号（その他）: PMID : 39566971
• DOI: 10.1248/cpb.c24-00465; https://doi.org/10.1248/cpb.c24-00465
• 関連情報（URI）: https://www.jstage.jst.go.jp/article/cpb/72/11/72_c24-00465/_pdf; https://search.jamas.or.jp/link/ui/2025314444
• 参照: Identification and optimization of piperlongumine analogues as potential antioxidant and anti-inflammatory agents via activation of Nrf2; https://cir.nii.ac.jp/crid/1360021000099741184; Discovery of a New Inhibitor of Myeloid Differentiation 2 from Cinnamamide Derivatives with Anti-Inflammatory Activity in Sepsis and Acute Lung Injury; https://cir.nii.ac.jp/crid/1360021000100044928; Inspired by magnolol: design of NSAID-based compounds with excellent anti-inflammatory effects; https://cir.nii.ac.jp/crid/1360021000100103680; Resveratrol-based cinnamic ester hybrids: synthesis, characterization, and anti-inflammatory activity; https://cir.nii.ac.jp/crid/1360021000100193664; Design, synthesis and evaluation of novel ferulic acid- O -alkylamine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease; https://cir.nii.ac.jp/crid/1360302474290063872; Insight into the Crystal Structures and Potential of Two Newly Synthesized Naproxen-Based Hydrazide Derivatives as Potent COX-2 Inhibitors; https://cir.nii.ac.jp/crid/1360302477006234496; New phenolic cinnamic acid derivatives as selective COX-2 inhibitors. Design, synthesis, biological activity and structure-activity relationships; https://cir.nii.ac.jp/crid/1360302477006354432; Synthesis and biological evaluation of curcumin derivatives containing NSAIDs for their anti-inflammatory activity; https://cir.nii.ac.jp/crid/1360302477006361856; Structurally Simple, Readily Available Peptidomimetic 1-Benzyl-5-methyl-4-(<i>n</i>-octylamino)pyrimidin-2(1<i>H</i>)-one Exhibited Efficient Cardioprotection in a Myocardial Ischemia (MI) Mouse Model; https://cir.nii.ac.jp/crid/1360302477006621696; Inflammasomes contributing to inflammation in arthritis; https://cir.nii.ac.jp/crid/1360579819773747712; Design, synthesis, and biological evaluation of a novel dual peroxisome proliferator-activated receptor alpha/delta agonist for the treatment of diabetic kidney disease through anti-inflammatory mechanisms; https://cir.nii.ac.jp/crid/1360583948546754816; Synthesis and in vitro characterization of naproxen derivatives as novel anti-inflammatory agents; https://cir.nii.ac.jp/crid/1360583948546860032; Hybrid Compounds Strategy in the Synthesis of Oleanolic Acid Skeleton-NSAID Derivatives; https://cir.nii.ac.jp/crid/1360583948547835648; Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation; https://cir.nii.ac.jp/crid/1360583948547838208; Pretreatment of Low-Dose and Super-Low-Dose LPS on the Production of<i>In Vitro</i>LPS-Induced Inflammatory Mediators; https://cir.nii.ac.jp/crid/1360861715041113600; Discovery of new cinnamic derivatives as anti‐inflammatory agents for treating acute lung injury in mice; https://cir.nii.ac.jp/crid/1360865424764849024; Non-steroidal anti-inflammatory drugs and risk of heart failure in four European countries: nested case-control study; https://cir.nii.ac.jp/crid/1360865424765973504; Naproxen-Derived New Compound Inhibits the NF-κB, MAPK and PI3K/Akt Signaling Pathways Synergistically with Resveratrol in RAW264.7 Cells; https://cir.nii.ac.jp/crid/1360865424766357632; Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen; https://cir.nii.ac.jp/crid/1360865424766369024; Inflammation in myocardial disease: From myocarditis to dilated cardiomyopathy; https://cir.nii.ac.jp/crid/1361412895701023744; Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations; https://cir.nii.ac.jp/crid/1361418518544038016; Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis; https://cir.nii.ac.jp/crid/1361699994813778048; Spatial confinement downsizes the inflammatory response of macrophages; https://cir.nii.ac.jp/crid/1361699995189064576; The protective effect of dexmedetomidine on LPS-induced acute lung injury through the HMGB1-mediated TLR4/NF-κB and PI3K/Akt/mTOR pathways; https://cir.nii.ac.jp/crid/1362262944092471296; Risk of acute myocardial infarction with NSAIDs in real world use: bayesian meta-analysis of individual patient data; https://cir.nii.ac.jp/crid/1362262944813202560; Mechanisms of Damage to the Gastrointestinal Tract From Nonsteroidal Anti-Inflammatory Drugs; https://cir.nii.ac.jp/crid/1363388845318481792; Inflammation as a central mechanism in Alzheimer's disease; https://cir.nii.ac.jp/crid/1363670318911652352; Inflammatory bowel disease: cause and immunobiology; https://cir.nii.ac.jp/crid/1363670320221358848; Inflammation and Cancer: Triggers, Mechanisms, and Consequences; https://cir.nii.ac.jp/crid/1363951794904908800; Inhibition of LPS-induced iNOS, COX-2 and cytokines expression by poncirin through the NF-κB inactivation in RAW 264.7 macrophage cells; https://cir.nii.ac.jp/crid/1390001204625616384; Studies on the fate of naproxen. II. Metabolic fate in various animals and man.; https://cir.nii.ac.jp/crid/1390282679147061376
• 連携機関・データベース: 国立情報学研究所 : CiNii Research; https://cir.nii.ac.jp/
• 提供元機関・データベース: Japan Link Center; https://japanlinkcenter.org/top; Crossref; https://www.crossref.org; PubMed; https://pubmed.ncbi.nlm.nih.gov

• 要約等: <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
• オンライン閲覧公開範囲: インターネット公開
• 連携機関・データベース: 科学技術振興機構 : J-STAGE; http://www.jstage.jst.go.jp