有机化学 ›› 2014, Vol. 34 ›› Issue (12): 2566-2571.DOI: 10.6023/cjoc201406026 上一篇    下一篇

研究简报

水杨酰氧基膦酸酯衍生物的微波辅助合成及抗肿瘤活性研究

杨家强a, 马俊a, 车万莉a, 李明刚a, 黎刚a, 宋宝安b   

  1. a. 遵义医学院药学院 遵义 563003;
    b. 贵州大学精细化工研究中心 贵阳 550025
  • 收稿日期:2014-06-18 修回日期:2014-07-17 发布日期:2014-08-11
  • 通讯作者: 杨家强 E-mail:yjqcn@126.com
  • 基金资助:

    贵州省科技厅基金(No.黔科合外G字[2014]7013)﹑贵州省教育厅(No.黔科合人才团队字[2012]03号)资助项目.

Microwave-Assisted Synthesis and Antitumor Activity of Salicyl Acyloxy Phosphonate Derivatives

Yang Jiaqianga, Ma Juna, Che Wanlia, Li Mingganga, Li Ganga, Song Baoanb   

  1. a. School of Pharmacy, Zunyi Medical College, Zunyi 563003;
    b. Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025
  • Received:2014-06-18 Revised:2014-07-17 Published:2014-08-11
  • Supported by:

    Project supported by the Technology Department of Guizhou Province (No. G[2014]7013), the Education Department of Guizhou Province (No. QJHRCTDZ-2012-03).

微波辅助下, 采用水杨酸与α-羟基膦酸酯在DCC/DMAP催化下酯化, 合成了12个结构新颖的水杨酰氧基膦酸酯衍生物, 其结构经IR, 1H NMR, 13C NMR及元素分析确认. 优化得最适微波合成条件: 以15 mL CH2Cl2为溶剂, 辐射功率800 W, 室温反应3.5 h, 有最好产率, 该方法具有反应时间较短、产率较高等优点. 四甲基偶氮唑蓝(MTT)法测试了目标化合物的抗肿瘤活性, 结果表明: 目标化合物对所测试的四种肿瘤细胞均有增殖抑制作用. 其中化合物2f对HEp-2的抑制活性 [IC50=(13.9±0.6) μmol/L]略低于对照药[IC50=(9.3±1.1) μmol/L], 化合物2k对EC-109的抑制活性[IC50=(8.5±0.9) μmol/L]接近对照药[IC50=(5.9±1.0) μmol/L].

关键词: 水杨酸, α-羟基膦酸酯, 微波辐射, 合成, 抗肿瘤活性

Twelve new salicyl acyloxy phosphonate derivatives were synthesized via microwave-assisted reactions of salicylic acid with α-hydroxyphosphonate in DCC/DMAP. The structures of the products were confirmed by elemental analysis, IR, 1H NMR and 13C NMR data. The suitable synthetic conditions were as follows: in 15 mL of CH2Cl2 with power 800 W at room temperature for 3.5 h. The cytotoxic activities of all compounds on A-549, SGC-7901, HEp-2 and EC-109 in vitro were evaluated by using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method, and some of them showed good antitumor activity. Among the active compounds, espectively, compound 2f had better inhibition effect on HEp-2 cells growth [IC50=(13.9±0.6) μmol/L], the IC50 values of compound 2k was (8.5±0.9) μmol/L against EC-109 cells, similar to cisplatin [IC50=(5.9±1.0) μmol/L].

Key words: salicylic acid, α-hydroxyphosphonate, microwave irradiation, synthesis, antitumor activity