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

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(IC₅₀>；50 μmol/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。

Abstract: 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 MTT 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.