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Discovery of novel 2-aryl-4-bis-amide imidazoles (ABAI) as anti-inflammatory agents for the treatment of inflammatory bowel diseases (IBD)

Authors :
Ling Li
Sijie Yuan
Lin Lin
Fang Yang
Ting Liu
Chenglong Xu
Huiting Zhao
Jingxuan Chen
Peihua Kuang
Ting Chen
Wenzhen Liao
Jianjun Chen
Source :
Bioorganic chemistry. 120
Publication Year :
2021

Abstract

A series of 2-Aryl-4-Bis-amide Imidazoles (ABAI-1 to 30) were designed as anti-inflammatory agents. These compounds were synthesized and evaluated for the in vitro anti-inflammatory activities (inhibition of NO production and release of inflammatory cytokines). Several compounds effectively inhibited NO production in lipopolysaccharide (LPS) induced RAW264.7 cells. Among them, ABAI-30 exhibited the highest NO-inhibitory effect (inhibition rate of 87% at 20 μM). The anti-inflammatory mechanism of ABAI-30 was examined and found to be inhibiting the TLR4-pp65 and NLRP3-caspase-1 signaling pathway, thus leading to the downregulation of IL6, IL-1β and TNFα at both transcriptional and translational levels. Importantly, ABAI-30 demonstrated high in vivo anti-inflammatory efficacy in a dextran sulfate sodium (DSS)-induced colitis mouse model without causing obvious toxicity. Collectively, our study provides a potent anti-inflammatory agent, which deserves further investigation as a novel therapeutic candidate for treating inflammatory bowel diseases.

Details

ISSN :
10902120
Volume :
120
Database :
OpenAIRE
Journal :
Bioorganic chemistry
Accession number :
edsair.doi.dedup.....b2636da876f96bb9d29409a0b437394f