有机化学 ›› 2017, Vol. 37 ›› Issue (4): 1000-1008.DOI: 10.6023/cjoc201611039 上一篇    下一篇

研究简报

含1-[4-二(4-氟苯)甲基]哌嗪及1,2,3-三唑官能团的二硫代氨基甲酸酯的合成及抗肿瘤活性研究

莫松, 丁勇, 张刚, 张震, 杓学蓓, 李清寒, 杨学军, 陈峰   

  1. 西南民族大学化学与环境保护工程学院 成都 610041
  • 收稿日期:2016-11-28 修回日期:2017-01-07 发布日期:2017-02-15
  • 通讯作者: 李清寒 E-mail:lqhchem@163.com
  • 基金资助:

    四川省科技厅科技支撑计划(No.2015NZ0033)、西南民族大学研究生创新基金(No.CX2016SZ063)资助项目.

Synthesis and Anti-tumor Activity Evaluation of a Novel Series of Dithiocarbamates Bearing 1,2,3-Triazole and [1-Bi(4-fluorophenyl)methyl]piperazine Unit

Mo Song, Ding Yong, Zhang Gang, Zhang Zhen, Shao Xuebei, Li Qinghan, Yang Xuejun, Chen Feng   

  1. College of Chemistry and Environmental Protection Engineering, Southwest University for Nationalities, Chengdu 610041
  • Received:2016-11-28 Revised:2017-01-07 Published:2017-02-15
  • Contact: 10.6023/cjoc201611039 E-mail:lqhchem@163.com
  • Supported by:

    Project supported by the Sichuan Provincial Department of Science and Technology Support Projects (No. 2015NZ0033) and the Southwest University for Nationalities Students Innovation and Entrepreneurship Training Fund (No. S201510656121).

以1-[二(4-氟苯)甲基]哌嗪、苄溴、二硫化碳及溴丙炔为原料,应用5 mol%的CuI为催化剂,DMF-H2O (VV=1∶1)为溶剂,在70 ℃反应4 h以34%~65%的收率制得了16个含有1-[4-二(4-氟苯)甲基哌嗪及1,2,3-三唑官能团的二硫代氨基甲酸酯衍生物. 合成的16个目标化合物通过熔点测定和质谱、红外光谱、元素分析及核磁共振氢谱分析对其结构进行确证. 经体外抗肿瘤活性测试表明,在20 μg/mL的浓度下,有14个化合物对CDC25B具有较好的抑制活性,其抑制率高达97.96%,IC50高达11.55 μg/mL. 在40 μmol·L-1的浓度下,6个二硫代氨基甲酸酯化合物对白血病HL-60细胞生长的抑制率和IC50分别可高达99.99%和12.11 μg/mL,对肺癌A-549肿瘤细胞生长的抑制率和IC50分别可高达93.91%和22.45 μg/mL.

关键词: 1-[二(4-氟苯)甲基]哌嗪, 1,2,3-三唑, 二硫代氨基甲酸酯, 有机合成, 抗肿瘤活性

Sixteen novel dithiocarbamates containing 1,2,3-trizaole and [1-bi(4-fluorophenyl)methyl]piperazine group were prepared via two steps starting from [1-bi(4-fluorophenyl)methyl]piperazine, propargyl bromide, methanedithione and sodium azide, using a very simple catalytic system composed of 5 mol% copper(I) iodide and DMF-H2O (VV=1∶1) as solvent at 70 ℃ for 4 h with moderate yield (34%~65%). The structures of the new compounds were characterized by IR, MS, 1H NMR, 13C NMR and elemental analysis. The bioactive assay for the newly prepared compounds manifested that fourteen dithiocarbamate derivatives exhibited good to excellent inhibitory activity against CDC25B in 20 μg/mL (inhibitiory rate up to 97.96%, IC50 value up to 11.55 μg/mL), and six dithiocarbamate derivatives exhibited excellent inhibitory activity against leukemia HL-60 and lung cancer A-549 cell in 40 μmol·L-1 (inhibitiory rate up to 99.99% and 93.91%, respectively; IC50 value up to 12.11 and 22.45 μg/mL, respectively).

Key words: 1-[bi(4-fluorophenyl)methyl]piperazine, 1,2,3-trizaole, carbodithioate, organic synthesis, antitumor activity