• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Toll样受体4（TLR4）抑制剂的设计、合成及抗类风湿性关节炎作用机制

Design, Synthesis, and Antirheumatoid Arthritis Mechanism of TLR4 Inhibitors.

作者信息

Zhou Shiyang, Xue Weiwei, Tan Jun

机构信息

Chongqing Chemical Industry Vocational College, Chongqing 401228, China.

School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China.

出版信息

ACS Omega. 2024 Aug 14;9(34):36232-36241. doi: 10.1021/acsomega.4c02344. eCollection 2024 Aug 27.

DOI:10.1021/acsomega.4c02344
PMID:39220494
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11359639/
Abstract

A total of 12 carbonyl compounds were synthesized, their lipopolysaccharide induced inhibition, and activity of RAW264.7 cells was evaluated. The most active compound inhibited RAW264.7 cells with IC value of 1.02 ± 0.08 μM. Compound significantly inhibited the release of TNF-α, IL-1β, and IL-6 in supernatant for RAW264.7 cells. In vivo collagen-induced arthritis model tests administered orally, compound showed effects similar to those of methotrexate in the positive control group. The preliminary mechanism study showed that compound had an effect on abnormal expression for TLR4, TNF-α, NF-κB protein, and genes related to inflammation signaling pathway in RAW264.7 cells. Meanwhile, compound showed a good affinity for the TLR4 receptor in molecular docking simulation. Therefore, compound may be a promising lead compound for the treatment of rheumatoid arthritis.

摘要

总共合成了12种羰基化合物，评估了它们对脂多糖诱导的RAW264.7细胞的抑制作用和活性。活性最高的化合物对RAW264.7细胞的抑制作用的IC值为1.02±0.08μM。该化合物显著抑制RAW264.7细胞上清液中TNF-α、IL-1β和IL-6的释放。在口服给药的体内胶原诱导性关节炎模型试验中，该化合物表现出与阳性对照组甲氨蝶呤相似的效果。初步机制研究表明，该化合物对RAW264.7细胞中TLR4、TNF-α、NF-κB蛋白以及炎症信号通路相关基因的异常表达有影响。同时，在分子对接模拟中，该化合物对TLR4受体表现出良好的亲和力。因此，该化合物可能是治疗类风湿性关节炎的一种有前景的先导化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/82512ed143ee/ao4c02344_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/7441e21adc49/ao4c02344_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/46b2a3e378d6/ao4c02344_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/0e16bbeb64ca/ao4c02344_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/cd403ef81e39/ao4c02344_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/4e890948a8b1/ao4c02344_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/8f9eeb6665a9/ao4c02344_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/15a4b0edb4a5/ao4c02344_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/093ade6c7a14/ao4c02344_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/5325a5a55c90/ao4c02344_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/82512ed143ee/ao4c02344_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/7441e21adc49/ao4c02344_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/46b2a3e378d6/ao4c02344_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/0e16bbeb64ca/ao4c02344_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/cd403ef81e39/ao4c02344_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/4e890948a8b1/ao4c02344_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/8f9eeb6665a9/ao4c02344_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/15a4b0edb4a5/ao4c02344_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/093ade6c7a14/ao4c02344_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/5325a5a55c90/ao4c02344_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ccd/11359639/82512ed143ee/ao4c02344_0009.jpg

相似文献

1
Design, Synthesis, and Antirheumatoid Arthritis Mechanism of TLR4 Inhibitors.Toll样受体4（TLR4）抑制剂的设计、合成及抗类风湿性关节炎作用机制
ACS Omega. 2024 Aug 14;9(34):36232-36241. doi: 10.1021/acsomega.4c02344. eCollection 2024 Aug 27.
2
Design, synthesis and anti-rheumatoid arthritis activity of target TLR4 inhibitors.设计、合成及靶向 TLR4 抑制剂的抗风湿关节炎活性
Bioorg Med Chem. 2024 Jan 1;97:117539. doi: 10.1016/j.bmc.2023.117539. Epub 2023 Nov 30.
3
Synthesis, activity and mechanism for double-ring conjugated enones.双环共轭烯酮的合成、活性及作用机制
Bioorg Med Chem Lett. 2021 Oct 1;49:128315. doi: 10.1016/j.bmcl.2021.128315. Epub 2021 Aug 11.
4
(E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one ameliorates the collagen-arthritis via blocking ERK/JNK and NF-κB signaling pathway.（E）-3-（3,4-二甲氧基苯基）-1-（5-羟基-2,2-二甲基-2H-色烯-6-基）丙-2-烯-1-酮通过阻断ERK/JNK和NF-κB信号通路改善胶原性关节炎。
Int Immunopharmacol. 2013 Dec;17(4):1125-33. doi: 10.1016/j.intimp.2013.10.001. Epub 2013 Oct 14.
5
The dichloromethane extract of Callicarpa longissima rich in diterpenoid phenols exerts anti-inflammatory effect via inhibiting the TLR4/NF-κB signaling pathway.富含二萜酚的长叶紫珠的二氯甲烷提取物通过抑制TLR4/NF-κB信号通路发挥抗炎作用。
J Ethnopharmacol. 2023 Apr 6;305:116124. doi: 10.1016/j.jep.2022.116124. Epub 2022 Dec 29.
6
Study on anti-inflammatory effect of Shangkehuangshui in vitro and in vivo based on TLR4/TLR2-NF-κB signaling pathway.基于 TLR4/TLR2-NF-κB 信号通路的商克黄水体内外抗炎作用研究。
J Ethnopharmacol. 2024 Apr 6;323:117709. doi: 10.1016/j.jep.2024.117709. Epub 2024 Jan 3.
7
Src homology 2 domain-containing inositol-5-phosphatase 1 (SHIP1) negatively regulates TLR4-mediated LPS response primarily through a phosphatase activity- and PI-3K-independent mechanism.含Src同源2结构域的肌醇-5-磷酸酶1（SHIP1）主要通过一种不依赖磷酸酶活性和PI-3K的机制负向调节TLR4介导的LPS反应。
Blood. 2005 Jun 15;105(12):4685-92. doi: 10.1182/blood-2005-01-0191. Epub 2005 Feb 8.
8
Chymotrypsin attenuates adjuvant-induced arthritis by downregulating TLR4, NF-κB, MMP-1, TNF-α, IL-1β, and IL-6 expression in Sprague-Dawley rats.在斯普拉格-道利大鼠中，胰凝乳蛋白酶通过下调Toll样受体4（TLR4）、核因子κB（NF-κB）、基质金属蛋白酶-1（MMP-1）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达来减轻佐剂诱导的关节炎。
Immunopharmacol Immunotoxicol. 2022 Dec;44(6):959-969. doi: 10.1080/08923973.2022.2093743. Epub 2022 Jul 11.
9
[Effect of moxibustion at "Zusanli"(ST36) and "Shenshu"(BL23) on miR-155-mediated TLR4/NF-κB signaling involving amelioration of synovitis in rheumatoid arthritis rats].艾灸“足三里”（ST36）和“肾俞”（BL23）对miR-155介导的TLR4/NF-κB信号通路的影响及对类风湿关节炎大鼠滑膜炎的改善作用
Zhen Ci Yan Jiu. 2021 Mar 25;46(3):194-200. doi: 10.13702/j.1000-0607.200377.
10
[Activity of Codonopsis canescens against rheumatoid arthritis based on TLRs/MAPKs/NF-κB signaling pathways and its mechanism].基于TLRs/MAPKs/NF-κB信号通路的灰毛党参抗类风湿性关节炎活性及其机制
Zhongguo Zhong Yao Za Zhi. 2022 Nov;47(22):6164-6174. doi: 10.19540/j.cnki.cjcmm.20220727.401.

引用本文的文献

1
Integrated Multi-Level Investigation of Friend Leukemia Integration 1 Transcription Factor as a Novel Immune-Inflammatory Biomarker in Rheumatoid Arthritis: Bridging Bioinformatics, Clinical Cohorts, and Mechanistic Validation.Friend白血病整合1转录因子作为类风湿性关节炎新型免疫炎症生物标志物的综合多层次研究：连接生物信息学、临床队列和机制验证
J Inflamm Res. 2025 Mar 3;18:3105-3123. doi: 10.2147/JIR.S507941. eCollection 2025.

本文引用的文献

1
Design, synthesis and anti-rheumatoid arthritis activity of target TLR4 inhibitors.设计、合成及靶向 TLR4 抑制剂的抗风湿关节炎活性
Bioorg Med Chem. 2024 Jan 1;97:117539. doi: 10.1016/j.bmc.2023.117539. Epub 2023 Nov 30.
2
α-Mangostin Inhibited M1 Polarization of Macrophages/Monocytes in Antigen-Induced Arthritis Mice by Up-Regulating Silent Information Regulator 1 and Peroxisome Proliferators-Activated Receptor γ Simultaneously.α-倒捻子素通过同时上调沉默信息调节因子 1 和过氧化物酶体增殖物激活受体 γ 抑制抗原诱导关节炎小鼠中巨噬细胞/单核细胞的 M1 极化。
Drug Des Devel Ther. 2023 Feb 23;17:563-577. doi: 10.2147/DDDT.S397914. eCollection 2023.
3
Design and Synthesis of Novel Double-Ring Conjugated Enones as Potent Anti-rheumatoid Arthritis Agents.
新型双环共轭烯酮作为强效抗类风湿性关节炎药物的设计与合成
ACS Omega. 2022 Nov 17;7(48):44065-44077. doi: 10.1021/acsomega.2c05492. eCollection 2022 Dec 6.
4
Synthesis, activity and mechanism for double-ring conjugated enones.双环共轭烯酮的合成、活性及作用机制
Bioorg Med Chem Lett. 2021 Oct 1;49:128315. doi: 10.1016/j.bmcl.2021.128315. Epub 2021 Aug 11.
5
Design, synthesis and anti-rheumatoid arthritis evaluation of double-ring conjugated enones.双环共轭烯酮的设计、合成及抗类风湿关节炎活性评价。
Bioorg Chem. 2021 Apr;109:104701. doi: 10.1016/j.bioorg.2021.104701. Epub 2021 Feb 9.
6
Synthesis and Biological Activities of Chemical Drugs for the Treatment of Rheumatoid Arthritis.类风湿关节炎治疗用化学药物的合成与生物活性。
Top Curr Chem (Cham). 2019 Sep 28;377(5):28. doi: 10.1007/s41061-019-0252-5.
7
Liquiritin from Glycyrrhiza uralensis Attenuating Rheumatoid Arthritis via Reducing Inflammation, Suppressing Angiogenesis, and Inhibiting MAPK Signaling Pathway.甘草亭酸通过减轻炎症、抑制血管生成和抑制 MAPK 信号通路来减轻类风湿性关节炎。
J Agric Food Chem. 2019 Mar 13;67(10):2856-2864. doi: 10.1021/acs.jafc.9b00185. Epub 2019 Mar 1.
8
Novel carboxylate-based glycolipids: TLR4 antagonism, MD-2 binding and self-assembly properties.新型羧酸酯基糖脂：TLR4 拮抗作用、MD-2 结合和自组装特性。
Sci Rep. 2019 Jan 29;9(1):919. doi: 10.1038/s41598-018-37421-w.
9
Licochalcone A from licorice root, an inhibitor of human hepatoma cell growth via induction of cell apoptosis and cell cycle arrest.甘草中的甘草查尔酮 A 通过诱导细胞凋亡和细胞周期阻滞抑制人肝癌细胞生长。
Food Chem Toxicol. 2018 Oct;120:407-417. doi: 10.1016/j.fct.2018.07.044. Epub 2018 Jul 25.
10
Chemical Profile and Anti-inflammatory Activity of Total Flavonoids from Fisch.Fisch. 总黄酮的化学特征及抗炎活性
Iran J Pharm Res. 2018 Spring;17(2):726-734.