Synthesis and Biological Evaluation of Novel Substituted Chalcone-piperazine Derivatives

Hui Gao, Xi Zheng, Ping Zhu, Si Wang, Chunping Wan, Gaoxiong Rao, Zewei Mao
2018 Youji huaxue  
a 云南中医学院中药学院 昆明 650500) ( b 云南中医学院第一附属医院中心实验室 昆明 650021) 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 1 H 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(IC 50 =3.81 μmol/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(IC 50 值分别为 0.54, 0.05 和 9.12 μmol/L). Abstract A series of novel substituted
more » ... 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 (IC 50 =3.81 μmol/L), and 4-bromo-4'-[N-(4'-methyl-2oxophenylethyl)-1-piperazinyl]chalcone (25) displayed good cytotoxic activity against A549, Hela and sk-ov-3 (IC 50 =0.54, 0.05 and 9.12 μmol/L, respectively).
doi:10.6023/cjoc201707034 fatcat:bx6jolizmbgnreev6y5ngnbsqe