摘要/Abstract

白藜芦醇又名芪三酚，是一种生物活性很强的茋类化合物.在前期研究基础上，采用活性亚结构拼接的方法，将白藜芦醇与查耳酮片段连接起来，以寻找活性较高的新型抗肿瘤分子.白藜芦醇经Vilsmeier甲酰化、Aldol缩合、哌嗪取代及酰胺化反应，设计合成了13个未见文献报道的白藜芦醇-查尔酮衍生物，其结构经IR、¹H NMR、¹³C NMR和HRMS确证.采用噻唑蓝（MTT）法对目标化合物的体外细胞毒活性进行测试，结果表明，该类化合物具有较强的体外细胞毒活性，特别是（E）-3-（2，4-二甲氧基-6-（（E）-4-甲氧基苯乙烯基）苯基-1-（4-（N-丙烯酰基）哌嗪-1-基）苯基丙烷-2-烯-1-酮（9）对肿瘤细胞株（A549和Hela）均表现出良好的体外细胞毒活性（IC₅₀值分别为0.26和7.35 μmol·L^-1）.并且，流式细胞技术分析表明化合物9能够显著诱导肿瘤细胞A549的凋亡.
关键词: 白藜芦醇-查尔酮, 酰胺衍生物, 合成, 细胞毒活性
Resveratrol is a type of natural phenol with a broad range of good biological activities. Based on former work, in order to look for new anticancer agents, a series of novel amide compounds between resveratrol and chalcone possessing piperazine moiety have been synthesized by connecting principle of active biological groups. The structures of compounds were characterized by IR, ¹H NMR, ¹³C NMR and HRMS, and in vitro cytotoxic activity was evaluated against a panel of human tumor cell lines (Hela, A549 and SGC7901) by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The results demonstrated that amide compounds contributed good cytotoxic activity. Especially, (E)-3-(2,4-dimethoxy-6-((E)-4-methoxystyryl)phenyl)-1-(4-(N-acryloyl)piperazin-1-yl)phenylprop-2-en-1-one (9) showed the best cytotoxic activity against A549 and Hela (IC₅₀=0.26 and 7.35 μmol·L^-1, respectively), and fluorescence-activated cell sorter (FACs) analysis showed that compound 9 significantly induced apoptosis in A549 cell.
Key words: resveratrol-chalcone, amide derivatives, synthesis, cytotoxic activity


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