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Design, synthesis and antitubulin activity of novel podophyllotoxin derivatives as potent anticancer agent

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Abstract

Twenty novel podophyllotoxin derivatives(1―20) were designed and synthesized. The anti-proliferation activities of these compounds were evaluated against three human cancer cell lines(HepG2, Calu-1 and MCF-7) using podophyllotoxin and Combretastatin A4(CA-4) as positive controls. Among all the compounds, compound 2 displayed more significant anti-proliferation activities against MCF-7 and Calu-1 cell lines and showed lower toxicity towards non-cancer cells. Furthermore, the cell cycle and apoptosis analysis results revealed that compound 2 can cause cell arrest at G2/M phase, leading to cancer cell apoptosis. Meanwhile, it can also reduce the adhesive ability of Calu-1 cells to fibronectin and laminin. The docking simulation results demonstrated that compound 10 can nicely bind to the colchicine site of tubulin. The podophyllotoxin derivatives are worthy to be further investigated to obtain more potent anti-cancer drugs.

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References

  1. Karikas G. A., J. Buon., 2010, 15(4), 627

    Google Scholar 

  2. Mishra B. B., Tiwari V. K., Eur. J. Med. Chem., 2011, 46, 4769

    Article  CAS  Google Scholar 

  3. Zhang P. N., Li Z. F., Zhao C. Q., Nat. Prod. Res. Dev., 2004, 16(1), 80

    CAS  Google Scholar 

  4. Gordaliza M., Clin. Transl. Oncol., 2007, 9(12), 767

    Article  CAS  Google Scholar 

  5. Shang H., Chen H., Zhao D. M., Tang X. W., Liu Y. F., Pan L., Cheng M. S., Arch. Pharm. Chem. Life Sci., 2012, 345(1), 43

    Article  CAS  Google Scholar 

  6. Bohlin L., Rosen B., Drug Discov. Today, 1996, 1(8), 343

    Article  CAS  Google Scholar 

  7. Kumar A., Kumar V., Alegria A. E., Malhotra S. V., Curr. Med. Chem., 2011, 18(25), 3853

    Article  CAS  Google Scholar 

  8. Sang C. Y., Liu J. F., Qin W. W., Zhao J., Hui L., Jin Y. X., Chen S. W., Eur. J. Med. Chem., 2013, 70, 59

    Article  CAS  Google Scholar 

  9. You Y., Curr. Pharm. Des., 2005, 11(13), 1695

    Article  CAS  Google Scholar 

  10. Liu Y. Q., Yang L., Tian X., Curr. Bioact. Compd., 2007, 3(1), 37

    Article  CAS  Google Scholar 

  11. Gordaliza M., Castro M. A., del Corral J. M., Feliciano A. S., Curr. Pharm. Des., 2000, 6(18), 1811

    Article  CAS  Google Scholar 

  12. Berkowitz D. B., Maeng J. H., Dantzig A. H., Shepard R. L. Norman B. H., J. Am. Chem. Soc., 1996, 118, 9426

    Article  CAS  Google Scholar 

  13. Kamal A., Tamboli J. R., Nayak V. L., Adil S. F., Vishnuvardhan M. V., Ramakrishna S., Bioorg. Med. Chem., 2014, 22(9), 2714

    Article  CAS  Google Scholar 

  14. Kamal A., Tamboli J. R., Vishnuvardhan M. V., Adil S. F., Nayak V. L., Bioorg. Med. Chem. Lett., 2013, 23, 273

    Article  CAS  Google Scholar 

  15. Kamal A., Suresh P., Ramaiah M. J., Srinivasa Reddy T., Kapavarapu R. K., Rao B. N., Imthiajali S., Lakshminarayan R. T., Bioorg. Med. Chem., 2013, 21(17), 5198

    Article  CAS  Google Scholar 

  16. Wang H. W., Nogales E., Nature, 2005, 435, 911

    Article  CAS  Google Scholar 

  17. Gourley M., Williamson J. S., Curr. Pharm. Des., 2000, 6, 417

    Article  CAS  Google Scholar 

  18. Lin C. M., Ho H. H., Pettit G. R., Hamel E., Biochemistry, 1989, 28(17), 6984

    Article  CAS  Google Scholar 

  19. Pettit G. R., Singh S. B., Hamel E., Lin C. M., Alberts D. S., Experientia, 1989, 45(2), 209

    Article  CAS  Google Scholar 

  20. Pettit G. R., Toki B., Herald D. L., Verdier-Pinard P., Boyd M. R., Hamel E., Pettit R. K., J. Med. Chem., 1998, 41(10), 1688

    Article  CAS  Google Scholar 

  21. Nam N. H., Curr. Med. Chem., 2003, 10(17), 1697

    Article  CAS  Google Scholar 

  22. Abad A., López Pérez J. L., del Olmo E., García-Fernández L. F., Francesch A., Trigili C., Barasoain I., Andreu J. M., Díaz J. F., San Feliciano A., J. Med. Chem., 2012, 55(15), 6724

    Article  CAS  Google Scholar 

  23. Castro M. A., del Corral J. M. M., Gordaliza M., García P. A., Gómez-Zurita M. A., García-Grávalos M. D., de la Lglesia-Vicente J., Gajate C., An F. Y., Mollinedo F., San Feliciano A., J. Med. Chem., 2004, 47(5), 1214

    Article  CAS  Google Scholar 

  24. Ettinger D. S., Finkelstein D. M., Ritch P. S., Lincoln S. T., Blum R. H., Lung Cancer, 2002, 37(3), 311

    Article  Google Scholar 

  25. Che C., Yang G. Q., Thiot C., Lacoste M. C., Currie J. C., Demeule M., Regina A., Beliveau R., Castaigne J. P., J. Med. Chem., 2010, 53(7), 2814

    Article  CAS  Google Scholar 

  26. Qian Y., Zhang H. J., Lv P. C., Zhu H. L., Bioorg. Med. Chem., 2010, 18(23), 8218

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Biofunction Molecule, College of Life Science and Cheimistry & Chemical Engineering, Jiangsu Second Normal University, Nanjing, 210013, P. R. China

    Lifei Bai, Renlei Wang & Guohua Xu

  2. The Third People’s Hospital of Zhangjiagang of Jiangsu Province, Zhangjiagang, 215611, P. R. China

    Ye Zou

Authors
  1. Lifei Bai
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  2. Renlei Wang
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  3. Ye Zou
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  4. Guohua Xu
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Corresponding author

Correspondence to Guohua Xu.

Additional information

Supported by the National Natural Science Foundation of China(No.21376112), the Natural Science Foundation of the Colleges and Universities in Jiangsu Province, China(No.13KJB350002) and the Natural Science Foundation of the Colleges and Universities Major Project in Jiangsu Province, China(No.15KJA350001).

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Bai, L., Wang, R., Zou, Y. et al. Design, synthesis and antitubulin activity of novel podophyllotoxin derivatives as potent anticancer agent. Chem. Res. Chin. Univ. 31, 964–969 (2015). https://doi.org/10.1007/s40242-015-5325-6

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  • DOI: https://doi.org/10.1007/s40242-015-5325-6

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