Discovery of novel Bis-amide analogue ST12 for the treatment of inflammatory bowel diseases (IBD) by inhibiting NLRP3 inflammasome activation

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2025-03-22 DOI:10.1016/j.bioorg.2025.108402

Zhiqiang Sun , Qinru Zang , Chenglong Xu , Xuewen Zhang , Zhenghui Kang , Yushe Yang , Ling Li , Jianjun Chen

引用次数: 0

Abstract

Herein, we designed and synthesized a series of novel bis-amide small molecule anti-inflammatory agents, among them, compound ST12 showed most potent anti-inflammatory activity. ST12 effectively inhibited the production of nitric oxide (NO) (inhibition rate of 52.67 ± 0.03 % at 10 μM) and downregulated the mRNA levels of proinflammatory cytokines iNOS, IL-6, IL-1β and TNF-α in lipopolysaccharide (LPS) induced RAW264.7 cells. Furthermore, mechanism studies suggest that compound ST12 exerted anti-inflammatory effects by inhibiting the activation of the NLRP3 inflammasome. Importantly, ST12 effectively ameliorated DSS-induced colitis in vivo. Taken together, ST12 is worthy of further investigation as a small molecule anti-inflammatory agent for treatment of inflammatory bowel diseases (IBD).

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.