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- W4294300712 abstract "As a complex pathogenesis driven by immune inflammatory factors and intestinal microbiota, the treatment of inflammatory bowel disease (IBD) may rely on the comprehensive regulation of these important pathogenic factors to reach a favorable therapeutic effect. In the current study, we discovered a series of imidazo[4,5-c]quinoline derivatives that potently and simultaneously inhibited two primary proinflammatory signaling pathways JAK/STAT and NF-κB. Especially, lead compound 8l showed potent inhibitory activities against interferon-stimulated genes (IC50: 3.3 nM) and NF-κB pathways (IC50: 150.7 nM) and decreased the release of various proinflammatory factors at the nanomolar level, including IL-6, IL-8, IL-1β, TNF-α, IL-12, and IFN-γ. In vivo, 8l produced a strong anti-inflammatory activity in both dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced acute enteritis models and restored the structural composition of gut microbiota. Collectively, this study provided valuable lead compounds for the treatment of IBD and revealed the great anti-inflammatory potential of the simultaneous suppression of JAK/STAT and NF-κB signals." @default.
- W4294300712 created "2022-09-02" @default.
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- W4294300712 date "2022-09-02" @default.
- W4294300712 modified "2023-10-14" @default.
- W4294300712 title "Discovery of Novel Imidazo[4,5-<i>c</i>]quinoline Derivatives to Treat Inflammatory Bowel Disease (IBD) by Inhibiting Multiple Proinflammatory Signaling Pathways and Restoring Intestinal Homeostasis" @default.
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- W4294300712 doi "https://doi.org/10.1021/acs.jmedchem.2c00390" @default.
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