摘要
为了寻找结构新颖的活性分子,采用活性亚结构拼接的方法,设计合成了24个未见文献报道的取代查尔酮-哌嗪衍生物,其结构经~1H NMR、^(13)C NMR和HRMS确证.分别采用小鼠巨噬细胞Raw 264.7炎症模型和噻唑蓝(MTT)法对目标化合物的体外抗炎活性和细胞毒活性进行测试,结果表明,查尔酮母核和哌嗪环上的取代基对化合物的生物活性有明显影响.特别是3,4,5-三甲氧基-4'-[N-(2-氧代丙基)-1-哌嗪基]查尔酮(11)能有效抑制NO的生成(IC50=3.81μmol/L),4-溴-4'-[N-(4'-甲基-2-氧代苯乙基)-1-哌嗪基]查尔酮(25)对三种肿瘤细胞株(Hela,A549和sk-ov-3)均表现出良好的体外细胞毒活性(IC50值分别为0.54,0.05和9.12μmol/L).
A series of novel substituted chalcone-piperazine derivatives have been synthesized, and screened in vitro anti-inflammatory in lipopolysaccharide（LPS）-stimulated RAW-264.7 macrophages and cytotoxic activity against 3 strains human tumor cell lines. The results demonstrated that the substituents of the core ring and the NH group of piperazine ring had obvious influences on biological activities. Especially, 3,4,5-trimethoxy-4＇-[N-（2-oxopropyl）-1-piperazinyl]chalcone（11）showed better inhibitory effect on the generation of NO（IC50=3.81 μmol/L）, and 4-bromo-4＇-[N-（4＇-methyl-2-oxophenylethyl）-1-piperazinyl]chalcone（25） displayed good cytotoxic activity against A549, Hela and sk-ov-3（IC50=0.54, 0.05 and 9.12 μmol/L, respectively）.
出处
《有机化学》
SCIE
CAS
CSCD
北大核心
2018年第3期684-691,共8页
Chinese Journal of Organic Chemistry
基金
supported by the National Natural Science Foundation of China(Nos.81560620,81460624)
the Application Basic Research Program of Yunnan Province(No.2014FZ078)
the Yunnan Provincial Science and Technology Department-Applied Basic Research Joint Special Funds of Yunnan University of Traditional Chinese Medicine[No.2017FF117(-023)]~~
关键词
查尔酮-哌嗪衍生物
抗炎活性
细胞毒活性
chalcone-piperazine derivatives
anti-inflammatory activity
cytotoxic activity
作者简介
Corresponding authors. E-mail： wanchunping1012@163.com;Corresponding authors. E-mail： maozw@ynutcm.edu.cn.
