化学
体内
药理学
结肠炎
炎症性肠病
下调和上调
TLR4型
脂多糖
体外
促炎细胞因子
消炎药
酰胺
炎症
生物化学
信号转导
免疫学
医学
生物
内科学
生物技术
基因
疾病
作者
Ling Li,Sijie Yuan,Lin Lin,Fang Yang,Ting Liu,Chenglong Xu,Hai Zhao,Jingxuan Chen,Peihua Kuang,Ting Chen,Wenzhen Liao,Jianjun Chen
标识
DOI:10.1016/j.bioorg.2022.105619
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI