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.