新型白藜芦醇-查尔酮酰胺衍生物的合成及其细胞毒活性（英文）

Synthesis and Cytotoxic Activity of Novel Resveratrol-Chalcone Amide Derivatives

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、^(13)C 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(IC_(50)值分别为0.26和7.35μmol·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.

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,^1 H NMR, ^13 C 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-2 H-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.