SIOC English
有机化学
高级检索

有机化学 >

2013 , Vol. 33 >Issue 05: 1026 - 1034

DOI: https://doi.org/10.6023/cjoc201211052

研究论文

水杨酰芳胺类化合物的设计、合成及体外抗肿瘤活性研究

  • 王杰 ,
  • 邬皓 ,
  • 李家明 ,
  • 许勤龙 ,
  • 何广卫 ,
  • 钟国琛 ,
  • 张艳春
展开
  • a 安徽中医学院药学院 安徽省现代中药重点实验室 合肥 230031;
    b 合肥医工医药有限公司 合肥 230059

收稿日期: 2012-12-03

  修回日期: 2013-01-15

  网络出版日期: 2013-01-21

基金资助

安徽省自然科学基金(No. 1208085MH128)、国家创新药物孵化基地(No. 2012ZX09401066)资助项目

收起

Design, Synthesis, and Biological Evaluation of N-Aryl-salicylamide Derivatives as Potential Antitumor Agents

  • Wang Jie ,
  • Wu Hao ,
  • Li Jiaming ,
  • Xu Qinlong ,
  • He Guangwei ,
  • Zhong Guochen ,
  • Zhang Yanchun
Expand
  • a Anhui Key Laboratory of Traditional Chinese Medicine, Department of Pharmacy, Anhui College of Traditional Chinese Medicine, Hefei 230031;
    b Hefei Medical Engineering Pharmaceutical Co, Ltd., Hefei 230059

Received date: 2012-12-03

  Revised date: 2013-01-15

  Online published: 2013-01-21

Fold

摘要

根据骨架迁跃原理, 设计并合成了一系列具有酪氨酸激酶抑制剂拉帕替尼(Lapatinib)和诺拉替尼(Neratinib)结构片段的水杨酰芳胺类化合物, 其结构均经IR, 1H NMR, 13C NMR和MS确证. 采用四甲基偶氮唑盐(MTT)法考察所合成化合物的体外抗肿瘤细胞(A549, MCF-7, SGC-7901, Bel-7402)活性. 结果表明, 所合成的化合物对4种肿瘤细胞增殖均有一定的抑制活性, 部分化合物的活性强于阳性对照药吉非替尼(Gefitinib).

关键词： 水杨酰芳胺; 酪氨酸激酶抑制剂; 抗肿瘤

本文引用格式

王杰 , 邬皓 , 李家明 , 许勤龙 , 何广卫 , 钟国琛 , 张艳春 . 水杨酰芳胺类化合物的设计、合成及体外抗肿瘤活性研究[J]. 有机化学, 2013 , 33(05) : 1026 -1034 . DOI: 10.6023/cjoc201211052

Abstract

According to the scaffold hopping, a series of N-aryl-salicylamide derivatives, which have fragments of tyrosine kinase inhibitors lapatinib and neratinib were designed and synthesized. Their structures were identified by IR, 1H NMR, 13C NMR and MS techniques. The target compounds were tested for cytotoxic activity against four cancer cell lines, including A549, MCF-7, SGC-7901, Bel-7402, by methyl thiazolyl tetrazolium (MTT) in vitro. All the compounds demonstrated certain antitumor abilities, and some of them were better than gefitinib.

Key words： N-aryl-salicylamide; tyrosine kinase inhibitors; antitumor

参考文献

[1] Zhao, X.; Guo, C.-B.; Zhou, H. Chin. J. Med. Chem. 2010, 20(5), 442 (in Chinese).
(赵欣, 郭长彬, 周化, 中国药物化学杂志, 2010, 20(5), 442.)
[2] Levitzki, A.; Klein, S. Mol. Aspects Med. 2010, 31(4), 287.
[3] Curigliano, G. Cancer Treat. Rev. 2012, 38(4), 303.
[4] Hoelder, S.; Clarke, P. A.; Workman, P. Mol. Oncol. 2012, 6(2), 155.
[5] Singh, J.; Petter, R. C.; Kluge, A. F. Curr. Opin. Chem. Biol. 2010, 14(4), 475.
[6] Dienstmann, R.; Dossob, S. D.; Felipa, E.; Taberneroa, J. Mol. Oncol. 2012, 15, 26.
[7] Kim, J. W.; Kim, H. P.; Kang, S.; Hur, H. S.; Yoon, Y. K.; Oh, D. Y.; Kim, J. H.; Lee, D. S.; Kim, T. Y.; Bang, Y. J. Cancer Lett. 2008, 272(2), 296.
[8] Slobbe, P.; Poot, A. J.; Windhorst, A. D.; Dongen, G. V. Drug Discovery Today 2012, 17(21-22), 1175.
[9] Dolezal, R.; Damme, S. V.; Bultinck, P.; Waisser, K. Eur. J. Med. Chem. 2009, 44(2), 869.
[10] Liechti, C.; Sequin, U.; Bold, G.; Furet, P.; Meyer, T.; Traxler, P. Eur. J. Med. Chem. 2004, 39(1), 11.
[11] Yang, Y.; Shi, L.; Zhou, Y.; Li, H.-Q.; Zhu, Z.-W.; Zhu, H.-L. Bioorg. Med. Chem. Lett. 2010, 20(22), 6653.
[12] Jin, Y.-L.; Lu, Z.-Z.; Ding, K.; Li, J.; Du, X.; Chen, C.; Sun, X.-Y.; Wu, Y.-B.; Zhou, J.; Pan, J.-X. Cancer Res. 2010, 70, 6 2516.
[13] Guo, L.; Wang, Q. L.; Jiang, Q. Q.; Jiang, Q. J.; Jiang, Y. B. J. Org. Chem. 2007, 72, 9947.
[14] Zhang, P.-X.; Mao, Y.-J.; Shen, J.-S.; Wei, Y.-B. Chin. J. Med. Chem. 2008, 18(5), 355 (in Chinese).
(张佩璇, 茆勇军, 沈敬山, 韦亚兵, 中国药物化学杂志, 2008, 18(5), 355.)
[15] Waissera, K.; Buresa, O.; Holya, P.; Kunesa, J.; Oswalda, R.; Jiraskova, L.; Poura, M.; Klimesova, V.; Kubicova, L.; Kaustovab, J. Arch. Pharm. Pharm. Med. Chem. 2003, 336(1), 53.
[16] Song, J.-P.; Zhong, P.; Wang, T.; Wei, X.-L.; Zhang, H. J. Cell Mol. Immunol. 2001, 17(3), 292 (in Chinese).
(宋锦平, 钟萍, 汪涛, 温秀兰, 张虹, 细胞与分子免疫学杂志, 2001, 17(3), 292.)
[17] Datki, Z.; Juhasz, A.; Galfi, M.; Soos, K.; Papp, R.; Zadori, D.; Penke, B. Brain Res. Bull. 2003, 62(3), 223.
Options
文章导航

/

〈 〉