摘要
目的设计合成新型2-芳基亚甲基-1-茚酮,评价这些化合物体外抑制LPS诱导的促炎因子TNF-α和IL-6的活性,并初步探讨化合物的抗炎构效关系。方法以6-羟基-1-茚酮为原料,经Aldol缩合、THP保护和脱保护反应,合成2-芳基亚甲基-1-茚酮;采用LPS刺激小鼠巨噬细胞释放促炎因子TNF-α和IL-6的筛选模型对合成的目标化合物抗炎活性进行评价。结果与结论合成了10个未见文献报道的新化合物;体外抗炎活性评价结果表明,大多数化合物能显著抑制炎症因子的释放,特别是化合物3h表现出较强的抗炎活性,可以作为抗炎类药物研发的候选化合物。
A series of novel 2-arylmethylene-l-indones were synthesized and their inhibitory activities against LPS-induced TNF-α and IL-6 release were evaluated, and the preliminary structure-activity relationships were discussed. The target compounds were synthesized via step method. The anti-inflarnmtory activities of 10 new compounds were evaluated by an enzyme-linked immunosorbent assay（ELISA）. Preliminary results showed that most of compounds effectively inhibited the LPS-induced expression of TNF-α and IL-6. In par- ticular ,compound 3h showed the strongest inhibitory potency amongst the tested compounds, and had the highest inhibition 64. 5 % （TNF-~） and 73.9% （ IL-6 ）, respectively.
作者
陈英英
邱胤达
陈慧珍
方博
陈显鑫
周俐娜
刘志国
顾禹归
CHEN Ying-ying;QIU Yin-da;CHEN Hui-zhen;FANG Bo;CHEN Xian-xin;ZHOU Li-na;LIU Zhi-guo;GU Yu-gui(College of Chemistry ＆Materials Engineering,Wenzhou University,Wenzhou 325035,China;College of Life and Environmental Science,Wenzhou University,Wenzhou 325035,China;School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou 325035,China)
出处
《中国药物化学杂志》
CAS
CSCD
北大核心
2018年第4期285-290,共6页
Chinese Journal of Medicinal Chemistry
基金
国家自然科学基金项目(81773579)
浙江省自然科学基金项目(LY17B020008)
关键词
2-芳基亚甲基-1-茚酮
抗炎活性
构效关系
2-arylmethylene-l-indones
anti-inflammtory activity
SAR （ structure-activity relationship）
