新型取代查尔酮-哌嗪衍生物的合成及其生物活性评价（英文）  

Synthesis and Biological Evaluation of Novel Substituted Chalcone-piperazine Derivatives

作　　者：高慧 郑喜[2] 朱萍 王斯 万春平[2] 饶高雄[1] 毛泽伟[1] 

机构地区：[1]云南中医学院中药学院,昆明650500 [2]云南中医学院第一附属医院中心实验室,昆明650021

出　　处：《有机化学》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)]~~

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）.

关 键 词：查尔酮-哌嗪衍生物 抗炎活性 细胞毒活性 

分 类 号：O626[理学—有机化学]