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Synthesis and biological evaluation of novel schisanhenol derivatives as potential hepatoprotective agents
European Journal of Medicinal Chemistry ( IF 6.7 ) Pub Date : 2021-10-12 , DOI: 10.1016/j.ejmech.2021.113919
Lulu Deng 1 , Shasha Cheng 1 , Jiang Li 1 , Xinglian Xu 1 , Xiaojiang Hao 1 , Yanhua Fan 1 , Shuzhen Mu 1
Affiliation  

Twenty-one new schisanhenol derivatives were synthesized, and their hepatoprotective effects against liver injury induced by concanavalin A (Con A) were evaluated in vitro using an MTT assay. The data indicated that most derivatives exhibited equivalent or better protective activity than the positive control (dimethyl dicarboxylate biphenyl, DDB) under the same conditions. Among them, compound 1b showed the most potent hepatoprotective activity against Con A-induced immunological injury. Mechanistic studies in vitro revealed that 1b inhibited cell apoptosis and inflammatory responses caused by Con A treatment via IL-6/JAK2/STAT3 signaling pathway. Consistently, it also exhibited significant hepatoprotective activity in mice with Con A-induced immunological liver injury. These results clearly indicated that 1b might be a highly potent hepatoprotective agent targeting IL-6/STAT3 signaling pathway.



中文翻译:

新型五味子酚衍生物作为潜在的保肝剂的合成和生物学评价

合成了 21 种新的五味子酚衍生物,并使用 MTT 法在体外评估了它们对刀豆蛋白 A (Con A) 诱导的肝损伤的保肝作用。数据表明,在相同条件下,大多数衍生物表现出与阳性对照(二羧酸联苯二甲酯,DDB)相当或更好的保护活性。其中,化合物1b对Con A诱导的免疫损伤表现出最有效的保肝活性。体外机制研究表明,1b抑制由 Con A 治疗引起细胞凋亡和炎症反应。IL-6/JAK2/STAT3 信号通路。一致地,它在 Con A 诱导的免疫性肝损伤小鼠中也表现出显着的肝保护活性。这些结果清楚地表明,1b可能是一种针对 IL-6/STAT3 信号通路的高效保肝剂。

更新日期:2021-10-21
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