选择性拮抗nod1介导的炎症信号通路减轻幽门螺杆菌感染引起的胃炎症

IF 6.8 1区医学 Q1 CHEMISTRY, MEDICINAL

Journal of Medicinal Chemistry Pub Date : 2024-12-05 DOI:10.1021/acs.jmedchem.4c02139

Xinhua Liu, Dan Wang, Xiduan Wei, Dan Yang, Yao Ma, Gang Liu

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引用次数: 0

摘要

幽门螺杆菌（h.p ylori）感染的特点是幽门螺杆菌和胃疾病之间复杂的相互作用。已经证实NOD1可被幽门螺杆菌细胞壁中的肽聚糖（PGN）激活，作为炎症的关键介质，启动RIP2/NF-κB和MAPK炎症信号通路。在这篇文章中，我们报道了2-氯喹唑啉-4-醇衍生物66作为人类和小鼠NOD1的有效和选择性拮抗剂的开发，该衍生物在免疫和上皮细胞中有效抑制炎症因子（IL-6, TNF-α）和趋化因子（CXCL1, CXCL8）的表达，以及在幽门螺旋杆菌诱导的小鼠胃炎模型中口服炎症因子（KC, IL-6）的表达。本研究为治疗幽门螺旋杆菌感染引起的胃炎奠定了基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Selectively Antagonizing the NOD1-Mediated Inflammatory Signaling Pathway Mitigates the Gastric Inflammation Induced by Helicobacter pylori Infection

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Selectively Antagonizing the NOD1-Mediated Inflammatory Signaling Pathway Mitigates the Gastric Inflammation Induced by Helicobacter pylori Infection

Helicobacter pylori (H. pylori) infection is characterized by the complex interplay between H. pylori and gastric disorders. It has been established that NOD1 can be activated by the peptidoglycan (PGN) present in the cell wall of H. pylori, serving as a key mediator of inflammation and initiating the RIP2/NF-κB and MAPK inflammatory signaling pathways. In this article, we reported on the development of a 2-chloroquinazolin-4-ol derivative 66 as a potent and selective antagonist of both human and mouse NOD1, which effectively inhibited the expression of inflammatory cytokines (IL-6, TNF-α) and chemokines (CXCL1, CXCL8) in immune and epithelial cells, as well as inflammatory cytokines (KC, IL-6) in a H. pylori-induced murine model of gastritis following oral administration. This study laid a foundation for treating gastritis induced by H. pylori infection.

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来源期刊

Journal of Medicinal Chemistry 医学-医药化学

CiteScore

4.00

自引率

11.00%

发文量

804

审稿时长

1.9 months

期刊介绍： The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.