摘要/Abstract

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、¹³C 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=3.81 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（IC₅₀值分别为0.54，0.05和9.12 μmol/L）.
关键词: 查尔酮-哌嗪衍生物, 抗炎活性, 细胞毒活性
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).
Key words: chalcone-piperazine derivatives, anti-inflammatory activity, cytotoxic activity


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