含氮芥和蒽环的新型α,β-不饱和酮的合成、表征与抗肿瘤活性  

Synthesis, Characterization and Anticancer Activity of Novel α,β-Unsaturated Ketones Contain Nitrogen Mustard and Anthracene

作　　者：黄伟婷 何露欣 李世晓 丘文桦 赵曦 王戴妮 龚晓璇 梁远维 HUANG Weiting;HE Luxin;LI Shixiao;QIU Wenhua;ZHAO Xi;WANG Daini;GONG Xiaoxuan;LIANG Yuanwei(College of Chemistry and Environment,Guangdong Ocean University,Zhanjiang 524088,China;Liaoning Keyuan Environmental Technology Co.,Ltd.,Shenyang 110161,China)

机构地区：[1]广东海洋大学化学与环境学院,广东湛江524088 [2]辽宁省环保集团科源环境技术有限公司,辽宁沈阳110161

出　　处：《合成化学》2023年第2期154-160,共7页Chinese Journal of Synthetic Chemistry

基　　金：广东省基础与应用基础研究基金资助项目(2019A1515110313);湛江市科技发展专项资金竞争性分配项目(2019A01012,2021A05045);广东海洋大学博士科研启动项目(R19057);大学生创新创业训练计划项目(CXXL2020291)。

摘　　要：为获得含氮芥和蒽环的α,β-不饱和酮衍生物及其体外抗肿瘤效果,结合Vilsmeier-Haack反应和羟醛缩合反应合成了两种新型含氮芥和蒽环的α,β-不饱和酮(1a和1b),其结构经^(1)H NMR、^(13)C NMR、 MS(ESI)和紫外和荧光光谱表征。采用MTT法检测了1a和1b对肺癌细胞A549、肾癌细胞786-O、宫颈癌细胞Hela和乳腺癌细胞MDA-MB-231增殖的抑制活性;采用细胞划痕实验检测了1a对Hela细胞转移的影响;采用流式细胞仪(PI染色)检测了1a对Hela细胞周期的影响。结果表明:1a和1b对4种肿瘤细胞均有良好的抗增殖活性,其中1a的活性略高于1b;1a能有效抑制Hela细胞转移,并使Hela细胞周期阻滞在S期。To obtain nitrogen mustard and anthracene containing α,β-unsaturated ketones and evaluate their anticancer activities, two novel α,β-unsaturated ketones 1a and 1b that contain nitrogen mustard and anthracene were synthesized by Vilsmeier-Haack reaction and hydroxyl aldehyde condensation reaction. Their structure was characterized by ^(1)H NMR,^(13)C NMR, MS(ESI), UV spectrum and fluorescence spectrum. MTT assay was used to detect the antiproliferative activities of 1a and 1b against lung cancer cell A549, kidney cancer cell 786-O, cervical cancer cell Hela and breast cancer cell MDA-MB-231. Wound healing assay was used to detect the effect of 1a on Hela cell metastasis. Flow cytometry(PI staining) was used to detect the effect of 1a on Hela cell cycle. The results showed that 1a and 1b both exerted good antiproliferative activity against the four tumor cells, and the activity of 1a was slightly stronger than that of 1b. In addition, 1a can effectively inhibit Hela cell metastasis and arrest Hela cell cycle in S phase. Therefore, the synthetic nitrogen mustard and anthracene containing α,β-unsaturated ketone derivatives have broad application prospects in antiproliferation and anti-metastasis.

关 键 词：蒽 氮芥 α β-不饱和酮 合成 Vilsmeier-Haack反应 抗肿瘤活性 细胞周期 

分 类 号：O621.2[理学—有机化学]