Articles

Design, Synthesis and Biological Activity of 1,2-Benzothiazine Derivatives as Potential Anticancer Agents

  • Wang Jie ,
  • Xu Qinlong ,
  • Li Jiaming ,
  • Zhang Enli ,
  • Hu Minhua ,
  • Ye Wenfeng ,
  • Huang Weijun
Expand
  • a. Anhui Key Laboratory of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230031;
    b. Medicinal Chemistry Department, Anhui Academy of Chinese Medicine, Hefei 230038;
    c. Hefei Industrial Pharmaceutical Institute Co., Ltd., Hefei 230059

Received date: 2014-02-17

  Revised date: 2014-04-27

  Online published: 2014-06-09

Supported by

Project supported by the Anhui Provincial Natural Science Foundation (No. 1208085MH128) and the National Incubator of Innovative Drugs (No. 2012ZX09401066).

Abstract

Thirteen 1,2-benzothiazine derivatives 5a11a, 5b10b have been designed and synthesized based on bioisosterism, and the structures of the target compounds were characterized by 1H NMR, 13C NMR, IR and mass spectra. The Anti-tumor activities of the target compounds against A549, A431, MDA-MB-468, HL60 cells in vitro were investigated by methyl thiazolyl tetrazolium (MTT) method. Most of the synthesized compounds were proved to have potent antitumor activity. Among them, compound 5b showed the most potent biological activity against A549 cell line with IC50 value of 1.57 μmol/L, compound 9a against A431, A549 and MDA-MB-468 had stronger cell growth inhibitory action than gefitinib. Molecular docking was performed to position compound 5b into epidermal growth factor receptor (EGFR) binding site in order to explore the potential target.

Cite this article

Wang Jie , Xu Qinlong , Li Jiaming , Zhang Enli , Hu Minhua , Ye Wenfeng , Huang Weijun . Design, Synthesis and Biological Activity of 1,2-Benzothiazine Derivatives as Potential Anticancer Agents[J]. Chinese Journal of Organic Chemistry, 2014 , 34(10) : 2040 -2046 . DOI: 10.6023/cjoc201402014

References

[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] Peter, W. A. Prog. Drug Res. 2011, 67, 175.
[6] Chiranjeevi, S.; Ricardo, M. P.; Sahar, A.; Vahid, E.; Glenn, B.; Steve, J.; James, R. R.; Joel, M. G.; Mark, A. P. Neurobiol. Dis. 2011, 42(3), 496.
[7] Mirzoeva, O. K.; Hann, B.; Hom, Y. K.; Debnath, J.; Aftab, D.; Shokat, K.; Korn, W. M. J. Mol. Med. 2011, 89(9), 877.
[8] Serova, M.; Gramont, A.; Raballand, A. T.; Santos, C. D.; Riveiro, M. E.; Slimane, K.; Faivre, S.; Raymond, E. Cancer Chemother. Pharmacol. 2013, 71(5), 1297.
[9] Coussens, L. M.; Werb, Z. Nature 2002, 420, 860.
[10] Chon, E.; McCartan, L.; Kubicek, L. N.; Vail, D. M. Vet. Comp. Oncol. 2012, 10(3), 184.
[11] Groot, D. J. A.; Vries, E. G. E.; Groen, H. J. M.; Jong, S. Crit. Rev. Oncol. Hemat. 2007, 61(1), 52.
[12] Ye, W. F.; He, C. F.; Li, J. M.; Xu, Q. L. Chin. J. New Drugs 2013, 22(23), 2765 ( in Chinese).
(叶文峰, 何从发, 李家明, 许勤龙, 中国新药杂志, 2013, 22(23), 2765.)
[13] Zhang, N.; Tao, K. X.; Huang, T. J. Huazhong Univ. Sci. Med. 2007, 27(4), 399.
[14] Naruse, T.; Nishida, Y.; Ishiguro, N. Biomed. Pharmacother 2007, 61(6), 338.
[15] Khalid, A.; Hamid, L. S.; Umar, F. R.; Saeed, A.; Masood, P. Acta Crystallogr., Sect. E 2010, E66, o862.
[16] Ahmad, I.; Abdullah, D. A. J. Saudi Chem. Soc. 2012.
[17] Liechti, C.; Sequin, U.; Bold, G.; Furet, P.; Meyer, T.; Traxler, P. Eur. J. Med. Chem. 2004, 39(1), 11.
[18] Yuan, M.; Li, J. M.; He, G. W.; Zhong, G. C.; Zhang, Y. C. Acta Pharm. Sinica 2013, 48(6), 874 (in Chinese).
(袁明, 李家明, 何广卫, 钟国琛, 张艳春, 药学学报, 2013, 48(6), 87.)
[19] Wang, J.; Wu, H.; Li, J. M.; Xu, Q. L.; He, G. W.; Zhong, G. C.; Zhang, Y. C. Chin. J. Org. Chem. 2013, 33, 1026 (in Chinese).
(王杰, 邬皓, 李家明, 许勤龙, 何广卫, 钟国琛, 张艳春, 有机化学, 2013, 33, 1026.)
[20] Jane, W.; David, L.; Jeff, C.; Gabriel, M.; James, G.; Michael, V. Bioorg. Med. Chem. Lett. 2010, 20(5), 1604.
[21] Schapira, C.; Perillo, I. A.; Lamdan, S. J. Heterocycl. Chem. 1980, 17, 1281.
[22] Rasmussen, C. R. J. Org. Chem. 1974, 39(11), 1554.
[23] Datki, Z.; Juhasz, A.; Galfi, M.; Soos, K.; Papp, R.; Zadori, D.; Penke, B. Brain Res. Bull. 2003, 62(3), 223.

Outlines

/