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Synthesis and In Vitro Anticancer Activity of Triazolyl Analogs of Podophyllotoxin, a Naturally Occurring Lignin

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Abstract

A series of triazolyl-modified podophyllotoxin analogs have been designed and synthesized by utilizing Huisgen 1,3-dipolar cycloaddition in order to develop potent antitumor agents. The synthesized analogs were assessed for in vitro anticancer activity against four human cancer cell lines, including MDA-MB-231 and MCF-7 (human breast cancer cells), A549 (human lung cancer), PC3 (human prostate cancer), and non-tumor human breast epithelial cell line FR2 by using MTT assay. Some of the tested derivatives exhibited potent biological profiles in comparison to podophyllotoxin. p-Nitrophenyltriazolyl and p-hydroxyphenyltriazolyl analogs were found to be the most potent with IC50 values of 19.0 (against PC3 cell line and 20.0 mM (against A549 cell line), respectively.

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REFERENCES

  1. Kelly, M.G. and Hartwell, J.L., J. Natl. Cancer Inst., 1954, vol. 14, p. 967. https://doi.org/10.1093/jnci/14.4.967

    Article  CAS  PubMed  Google Scholar 

  2. Imbert, T.F., Biochimie, 1998, vol. 80, p. 207. https://doi.org/10.1016/S0300-9084(98)80004-7

    Article  CAS  PubMed  Google Scholar 

  3. Canel, C., Moraes, R.M., Dayan, F.E., and Ferreira, D., Phytochemistry, 2000, vol. 54, p. 115. https://doi.org/10.1016/S0031-9422(00)00094-7

    Article  CAS  PubMed  Google Scholar 

  4. Garcia, E S. and Azambuja, P., Toxicon, 2004, vol. 44, p. 431. https://doi.org/10.1016/j.toxicon.2004.05.007

    Article  CAS  PubMed  Google Scholar 

  5. Williams, A.H.W., Dai, X.D., Blot, W., Xu, Z.Y., Sun, X.W., Xiao, H.P., Stone, B.J., Yu, S.F., Feng, Y.P., and Ershow, A.G., Br. J. Cancer, 1990, vol. 62, p. 982. https://doi.org/10.1038/bjc.1990.421

    Article  Google Scholar 

  6. Kamal, A., Tamboli, J.R., Nayak, V.L., Adil, S.F., Vishnu­vardhan, M.V.P.S., and Ramakrishna, S., Bioorg. Med. Chem., 2014, vol. 22, p. 2714. https://doi.org/10.1016/j.bmc.2014.03.021

    Article  CAS  PubMed  Google Scholar 

  7. Zhou, J., Qu, Z., Yan, S., Sun, F., Whitsett, J.A., Shapiro, S.D., and Xiao, G., Oncogene, 2015, vol. 34, p. 3804. https://doi.org/10.1038/onc.2014.318

    Article  CAS  PubMed  Google Scholar 

  8. Utsugi, T., Shibata, J., Sugimoto, Y., Aoyagi, K., Wierzba, K., Kobunani, T., Terada, T., Ohhara, T., Tsuruo, T., and Yamada, Y., Cancer Res., 1996, vol. 56, p. 2809.

    CAS  PubMed  Google Scholar 

  9. Subrahmanyam, D., Renuka, B., Rao, C.B., Sagar, P.S., Deevi, D.S., Babu, J.M., and Vyas, K., Bioorg. Med. Chem. Lett., 1998, vol. 8, p. 1391. https://doi.org/10.1016/S0960-894X(98)00232-7

    Article  CAS  PubMed  Google Scholar 

  10. Wang, J.Z., Tian, X., Tsumura, H., Shimura, K., and Ito, H., Anti-Cancer Drug Des., 1993, vol. 8, p. 193.

    CAS  Google Scholar 

  11. Huang, T.S., Lee, C.C., Chao, Y., Shu, C.H., Chen, L.T., Chen, L.L., Chen, M.H., Yuan, C.C., and Wang-Peng, J., Pharm. Res., 1999, vol. 16, p. 997. https://doi.org/10.1023/A:1018971313256

    Article  CAS  PubMed  Google Scholar 

  12. Gordaliza, M., Garcı́a, P.A., Miguel del Corral, J.M., Castro, M.A., and Gómez-Zurita, M.A., Toxicon, 2004, vol. 44, p. 441. https://doi.org/10.1016/j.toxicon.2004.05.008

    Article  CAS  PubMed  Google Scholar 

  13. Xu, H., Lv, M., and Tian, X., Curr. Med. Chem., 2009, vol. 23, p. 327. https://doi.org/10.2174/092986709787002682

    Article  Google Scholar 

  14. You, Y.J., Curr. Pharm. Des., 2005, vol. 11, p. 1695. https://doi.org/10.2174/1381612053764724

    Article  CAS  PubMed  Google Scholar 

  15. Lv, M., Xu, H., Mini-Rev. Med. Chem., 2011, vol. 11, p. 901. https://doi.org/10.2174/138955711796575461

    Article  CAS  PubMed  Google Scholar 

  16. Zhang, X., Rakesh, K.P., Shantharam, C.S., Asiri, A.M., Marwani, H.M., and Qin, H.L., Bioorg. Med. Chem., 2018, vol. 26, p. 340. https://doi.org/10.1016/j.bmc.2017.11.026

    Article  CAS  PubMed  Google Scholar 

  17. Mukherjee, A.K., Basu, S., Sarkar, N., and Ghosh, A.C., Curr. Med. Chem., 2001, vol. 8, p. 1467. https://doi.org/10.2174/0929867013372094

    Article  CAS  PubMed  Google Scholar 

  18. Stähelin, H.F., Eur. J. Cancer, 1973, vol. 9, p. 215. https://doi.org/10.1016/S0014-2964(73)80021-0

    Article  PubMed  Google Scholar 

  19. Hande, K.R., Eur. J. Cancer, 1998, vol. 34, p. 1514. https://doi.org/10.1016/S0959-8049(98)00228-7

    Article  CAS  PubMed  Google Scholar 

  20. Sanghvi, Y.S., Bhattacharya, B.K., Kini, G.D., Matsu­moto, S.S., Larson, S.B., Jolley, W.B., Robins, R.K., and Revankar, G.R., J. Med. Chem., 1990, vol. 33, p. 336. https://doi.org/10.1021/jm00163a054

    Article  CAS  PubMed  Google Scholar 

  21. Pawelec, G., Ehninger, G., Rehbein, A., Schaudt, K., and Jaschonek, K., Int. J. Immunopharmacol., 1991, vol. 13, p. 299. https://doi.org/10.1016/0192-0561(91)90111-J

    Article  CAS  PubMed  Google Scholar 

  22. Yan, S.J., Liu, Y.J., Jiang, Y., Chen, Y.L., Liu, L., and Lin, J., Bioorg. Med. Chem. Lett., 2010, vol. 20, p. 5225. https://doi.org/10.1016/j.bmcl.2010.06.141

    Article  CAS  PubMed  Google Scholar 

  23. Shaw, J., Chen, B., Bourgault, J.P., Jiang, H., Kumar, N., Mishra, J., Valeriote, F.A., Media, J., Bobbitt, K., Pietraszkiewicz, H., Edelstein, M., and Andreana, P.R., Am. J. Biomed. Sci., 2012, vol. 4, p. 14. https://doi.org/10.5099/aj120100014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Kumbhare, R.M., Kosurkar, U.B., Ramaiah, M.J., Dadmal, T.L., Pushpavalli, S.N.C.V.L., and PalBhadra, M., Bioorg. Med. Chem. Lett., 2012, vol. 22, p. 5424. https://doi.org/10.1016/j.bmcl.2012.07.041

    Article  CAS  PubMed  Google Scholar 

  25. Zhou, C.H. and Wang, Y., Curr. Med. Chem., 2012, vol. 19, p. 239. https://doi.org/10.2174/092986712803414213

    Article  CAS  PubMed  Google Scholar 

  26. Bhat, B.A., Reddy, P.B., Agrawal, S.K., Saxena, A.K., Kumar, H.M.S., and Qazi, G.N., Eur. J. Med. Chem., 2008, vol. 43, p. 2067. https://doi.org/10.1016/j.ejmech.2007.09.015

    Article  CAS  PubMed  Google Scholar 

  27. Reddy, P.B., Paul, D.V., Agrawal, S.K., Saxena, A.K., Kumar, H.M.S., and Qazi, G.N., Arch. Pharm., 2008, vol. 341, p. 126. https://doi.org/10.1002/ardp.200700116

    Article  CAS  Google Scholar 

  28. Reddy, D.M., Srinivas, J., Chashoo, G., Saxena, A.K., and Sampath Kumar, H.M., Eur. J. Med. Chem., 2011, vol. 46, p. 1983. https://doi.org/10.1016/j.ejmech.2011.02.016

    Article  CAS  PubMed  Google Scholar 

  29. Zi, C.T., Xu, F.Q., Li, G.T., Li, Y., Ding, Z.T., Zhou, J., Jiang, Z.H., and Hu, J.M., Molecules, 2013, vol. 18, p. 13992. https://doi.org/10.3390/molecules181113992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rashid, S., Bhat, B.A., and Mehta, G., Org. Lett., 2015, vol. 17, p. 3604. https://doi.org/10.1021/acs.orglett.5b01707

    Article  CAS  PubMed  Google Scholar 

  31. Rashid, S., Bhat, B.A., and Mehta, G., Tetrahedron Lett., 2017, vol. 58, p. 3800. https://doi.org/10.1016/j.tetlet.2017.08.026

    Article  CAS  Google Scholar 

  32. Rashid, S., Bhat, B.A., and Mehta, G., Tetrahedron Lett., 2019, vol. 60, p. 1122. https://doi.org/10.1016/j.tetlet.2019.03.037

    Article  CAS  Google Scholar 

  33. Rashid, S., Bhat, B.A., Sengupta, S., and Mehta, G., Asian J. Org. Chem., 2020, vol. 9, p. 449. https://doi.org/10.1002/ajoc.201900714

    Article  CAS  Google Scholar 

  34. Rashid, S., Bhat, B.A., and Mehta, G., Asian J. Org. Chem., 2020, vol. 9, p. 1726. https://doi.org/10.1002/ajoc.202000401

    Article  CAS  Google Scholar 

  35. Lone, A.M., Dar, N.A., Hamid, A., Shah, W.A., Ahmad, M., and Bhat, B.A., ACS Chem. Neurosci., 2016, vol. 7, p. 82. https://doi.org/10.1021/acschemneuro.5b00267

    Article  CAS  PubMed  Google Scholar 

  36. Masood-ur-Rahman, Mohammad, Y., Fazili, K.M., Bhat, K.A., and Ara, T., Steroids, 2017, vol. 118, p. 1. https://doi.org/10.1016/j.steroids.2016.11.003

    Article  CAS  PubMed  Google Scholar 

  37. Wang, Y., Shao, Y., Wang, Y., Fan, L., Yu, X., Zhi, X., Yang, C., Qu, H., Yao, X., and Xu, H., J. Agric. Food Chem., 2012, vol. 60, p. 8435. https://doi.org/10.1021/jf303069v

    Article  CAS  PubMed  Google Scholar 

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ACKNOWLEDGMENTS

B.A.G is highly thankful to Director NIT Srinagar for providing all types of facilities. B.A.G. also acknowledges Ministry of Human Resource Development (MHRD), New Delhi, for providing the Institute fellowship to carry out this work.

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Authors and Affiliations

  1. National Institute of Technology Hazratbal, 190006, Srinagar, Jammu & Kashmir, India

    B. A. Ganaie, J. A. Banday & T. Ara

  2. CSIR-Medicinal Chemistry Division, Indian Institute of Integrative Medicine Sanat Nagar, 190005, Srinagar, Jammu & Kashmir, India

    B. A. Bhat

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  1. B. A. Ganaie
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Ganaie, B.A., Banday, J.A., Bhat, B.A. et al. Synthesis and In Vitro Anticancer Activity of Triazolyl Analogs of Podophyllotoxin, a Naturally Occurring Lignin. Russ J Org Chem 57, 2039–2047 (2021). https://doi.org/10.1134/S1070428021120216

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