有机化学 ›› 2018, Vol. 38 ›› Issue (6): 1516-1524.DOI: 10.6023/cjoc201712018 上一篇    下一篇

研究论文

二萘并呋喃衍生物的合成及其抗肿瘤活性研究

宋永彬a,b, 李丹b, 杨异卉b, 纪红蕊a, 刘波a   

  1. a 哈尔滨理工大学化学与环境工程学院 哈尔滨 150040;
    b 哈尔滨医科大学药学院 哈尔滨 150081
  • 收稿日期:2017-12-10 修回日期:2018-01-22 出版日期:2018-06-25 发布日期:2018-02-06
  • 通讯作者: 杨异卉,E-mail:yangyihui19790508@sina.com E-mail:yangyihui19790508@sina.com
  • 基金资助:

    黑龙江省青年科学基金(No.QC2014C091)、黑龙江省普通本科高等学校青年创新人才培养计划(No.324015507)、黑龙江省博士后科研启动金(No.LBH-Q16187)资助项目.

Synthesis and Cytotoxicity of Dinaphtho [2, 1-b: 1', 2'-d]furan Derivatives

Song Yongbina,b, Li Danb, Yang Yihuib, Ji Hongruia, Liu Boa   

  1. a School of Chemical and Environmental Engineering, Harbin University of Science and Technology, Harbin 150040;
    b College of Pharmacy, Harbin Medical University, Harbin 150081
  • Received:2017-12-10 Revised:2018-01-22 Online:2018-06-25 Published:2018-02-06
  • Contact: 10.6023/cjoc201712018 E-mail:yangyihui19790508@sina.com
  • Supported by:

    Project supported by the Youth Science Fund of Heilongjiang Province (No. QC2014C091), the University Nursing Program for Young Scholars with Creative Talents in Heilongjiang Province (No. 324015507) and the Heilongjiang Postdoctoral Scientific Research Developmental Fund (No. LBH-Q16187).

为了研究二萘并呋喃衍生物的构效关系,设计合成了两个系列的二萘[2,1-b:1',2'-d]呋喃衍生物,通过1H NMR、13C NMR、HRMS和IR数据对所有目标化合物进行了结构鉴定.通过噻唑蓝(MTT)法测试了目标化合物的体外抗肿瘤活性,大多数化合物对人肝癌细胞(HepG2和SMMC-7721)、人宫颈癌细胞(HeLa细胞)和急性早幼粒细胞白血病细胞(NB4细胞)显示了较强的抗肿瘤活性.其中N3N11-二羟基二萘并[2,1-b:1',2'-d]呋喃-3,11-二甲酰胺(13k)对SMMC-7721细胞显示了很强抑制作用,其半数抑制浓度为0.57 μmol·L-1,远低于阳性对照药5-氟脲嘧定的20.21 μmol·L-1.

关键词: 合成设计, 细胞毒, 二萘并呋喃, 核磁光谱

In order to study the structure-activity relationships of dinaphthofuran derivatives, two series of dinaphtho[2,1-b:1', 2'-d]furan derivatives were synthesized. The structures of all compounds were identified by 1H NMR, 13C NMR, HRMS and IR spectra. The in vitro antitumor activity of the synthesized derivatives was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Most of them exhibited strong inhibitory activity on human hepatocellular carcinoma cell lines (HepG2 and SMMC-7721 cells), uterine cervix cancer Hela cells and acute promyelocytic leukemia NB4 cells. Compound 13k exhibited significant inhibitory activity against SMMC-7721 cells with IC50 vaue of 0.57 μmol·L-1, much lower than 20.21 μmol·L-1 of the positive control 5-Fu.

Key words: synthesis design, cytotoxicity, dinaphthofuran, NMR spectroscopy