甲酰胺
促炎细胞因子
败血症
药理学
体内
肿瘤坏死因子α
脂多糖
化学
炎症
医学
免疫学
生物化学
生物
生物技术
作者
Jun Yang,Minxiu Wang,Yulan Xu,Jing Liao,Xiang Li,Ying Zhou,Jintian Dai,Xiaobo Li,Pan Chen,Gaozhi Chen,Won‐Jea Cho,Nipon Chattipakorn,А. В. Самородов,В. Н. Павлов,Li Wang,Guang Liang,Qidong Tang
标识
DOI:10.1016/j.ejmech.2023.115144
摘要
Acute lung injury (ALI) and sepsis, characterized by systemic inflammatory response syndrome, remain the major causes of death in severe patients. Inhibiting the release of proinflammatory cytokines is considered to be a promising method for the treatment of inflammation-related diseases. In this study, a total of 28 4-oxo-N-phenyl-1,4-dihydroquinoline-3-carboxamide derivatives were designed and synthesized and their anti-inflammatory activities in J774A.1 were evaluated. Among them, derivative 13a was found to significantly inhibit lipopolysaccharide (LPS)-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) on J774A.1, THP-1 and LX-2 cells, and inhibited the activation of the NF-κB pathway. Furthermore, administration of 13ain vivo significantly improved the symptoms in LPS-induced ALI mice, including alleviation of pathological changes in the lung tissue, reduction of pulmonary edema, and inhibition of macrophage infiltration. Moreover, the administration of 13ain vivo significantly promoted survival in LPS-induced sepsis mice. 13a demonstrated favorable pharmacokinetic properties with T1/2 value of 11.8 h and F value of 36.3%. Therefore, this study has identified a novel 4-oxo-N-phenyl-1,4-dihydroquinoline-3-carboxamide derivative, 13a, which is an effective anti-inflammatory agent. The findings have laid a foundation for the further development of agents to treat ALI and sepsis.
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