类查尔酮Nrf2激活剂的合成及ARE诱导活性  

Synthesis and biological activity of chalcone derivatives as potent activators of Nrf2

作　　者：胡文渊[1,2] 陈婕[3] 姜正羽 王亚楼[1,2] 尤启冬[1,2] 

机构地区：[1]中国药科大学江苏省药物分子设计与成药性优化重点实验室,南京210009 [2]中国药科大学药物化学教研室,南京210009 [3]合肥市第八中学,合肥230071

出　　处：《中国药科大学学报》2016年第6期666-672,共7页Journal of China Pharmaceutical University

基　　金：supported by the National Natural Science Foundation of China(No.81230078;No.81573346)

摘　　要：对先导化合物CPUY191001结构进行改造,以期得到活性更好的ARE-Nrf2激活剂。通过羟醛缩合反应合成17个目标化合物,采用MTT法测试目标化合物的抗增殖活性,并利用荧光素酶报告基因实验考察目标化合物对ARE的诱导活性。MTT数据显示,该系列化合物几乎无细胞毒性(IC_(50)>50μmol/L),活性测试结果表明,大部分类查尔酮衍生物对ARE具有一定的诱导活性,其中化合物2,3,10活性较优,且具有浓度依赖性。化合物2,3,10在抗炎与肿瘤预防治疗药物的研究领域中具有一定的应用前景,值得进一步研究。To obtain ARE-Nrf2 potent activators through modifying the structure of the lead compound CPUY191001. 17 compounds were synthesized by aldol condensation, their cytotoxicity were tested using MTF assay, and ARE inductivity of these target compounds were analyzed by luciferase reporter gene assay. The biological evaluation results showed that most synthesized chalcone derivatives nearly had no cytotoxicity, and compounds 2, 3, 10 conducted better activity and in concentration-dependent manner. Compounds 2, 3, 10 are potential agents in the development of anti-inflammatory and chemoprevention, suggesting that compounds 2, 3, 10 are worth for further investigation.

关 键 词：查尔酮 NRF2 KEAP1 ARE 诱导活性 

分 类 号：R914.5[医药卫生—药物化学]