Chemistry of Natural Compounds

, Volume 55, Issue 5, pp 883–889 | Cite as

Synthesis and Cytotoxicity of A-Azepanodammaradiene

  • I. E. SmirnovaEmail author
  • A. V. Petrova
  • O. B. Kazakova

Sequential transformations of dipterocarpol (oximation, first-order Beckmann rearrangement, dehydration, isomerization) synthesized the new dammarane-type triterpenoid A-azepanodammara-20(21),24(25)-diene. Its cytotoxicity was studied in vitro against 60 cell lines of 9 human tumor types. The cytotoxicity against all cancer cell types increased significantly as compared to native dipterocarpol if an azepane fragment was introduced into ring A (percent inhibition from 15.72% to 82.08%). Detailed cytotoxicity studies confirmed the activity against a broad spectrum of human tumor cell lines with a mean (MID) log LC50 of 5.57.


dammarane triterpenoids dipterocarpol azepanes cytotoxicity 



The work was performed on State Task Topic No. AAAA-A17-117011910023-2. We thank the National Cancer Institute for determining the in vitro antitumor activity of 1 and 35.


  1. 1.
    H. Zhang, P. Zhu, J. Liu, X. Yang, S. Xu, H. Yao, J. Jiang, W. Ye, X. Wu, and J. Xu, Eur. J. Med. Chem., 87, 159 (2014).CrossRefGoogle Scholar
  2. 2.
    R. Mukherjee, M. Jaggi, P. Rajendran, M. J. Siddiqui, S. K. Srivastava, A. Vardhan, and A. C. Burman, Bioorg. Med. Chem. Lett., 14, 2181 (2004).CrossRefGoogle Scholar
  3. 3.
    R. W. Zhang, W. Wang, H. Wang, and Y. Zhao, “Novel Ginsenoside Compounds, Compositions, and Methods of Use,” WO076900A1 (2008).Google Scholar
  4. 4.
    G. Chen, W. Song, X. Yang, H. Ge, and J. Li, “Protopanaxadiol Derivative and Application Thereof,” CN103387596A (2013).Google Scholar
  5. 5.
    G.-F. Zha, K. P. Rakesh, H. M. Manukumar, C. S. Shantharam, and S. E. Long, J. Med. Chem., 162, 465 (2019).CrossRefGoogle Scholar
  6. 6.
    N. I. Medvedeva, O. B. Kazakova, T. V. Lopatina, I. E. Smirnova, G. V. Giniyatullina, I. P. Baikova, and V. E. Kataev, J. Med. Chem., 143, 464 (2018).CrossRefGoogle Scholar
  7. 7.
    O. B. Kazakova, G. V. Giniyatullina, N. I. Medvedeva, T. V. Lopatina, I. P. Baikova, G. A. Tolstikov, and G. N. Apryshko, Bioorg. Khim., 40, 217 (2014).PubMedGoogle Scholar
  8. 8.
    E. F. Khusnutdinova, I. E. Smirnova, G. V. Giniyatullina, N. I. Medvedeva, E. Y. Yamansarov, D. V. Kazakov, O. B. Kazakova, P. T. Linh, Q. Viet, and D. T. Huong, Nat. Prod. Commun., 11, 33 (2016).PubMedGoogle Scholar
  9. 9.
    M. Ukiya, T. Kikuchi, H. Tokuda, K. Tabata, Y. Kimura, T. Arai, Y. Ezaki, O. Oseto, T. Suzuki, and T. Akihisha, Chem. Biodiversity, 7, 1871 (2017).CrossRefGoogle Scholar
  10. 10.
    T. Akihisia, H. Tokuda, M. Ukiya, T. Suzuki, Enjo, K. Koike, T. Nikado, and H. Nishino, Chem. Pharm. Bull., 52, 153 (2004).CrossRefGoogle Scholar
  11. 11.
    K. Hjrabayashi, S. Iwata, and H. Matsumoto, Chem. Pharm. Bull., 39, 112 (1991).CrossRefGoogle Scholar
  12. 12.
    F. Inada, M. Somekawa, and H. Murata, Chem. Pharm. Bull., 41, 617 (1993).CrossRefGoogle Scholar
  13. 13.
    G. V. Platonov, A. D. Zorina, M. A. Gordon, N. P. Chizhov, L. V. Balykina, Yu. D. Mikhailov, D. R. Ivanen, Tran Kim Kvi, and A. G. Shavva, Khim.-farm. Zh., 2, 42 (1995).Google Scholar
  14. 14.
    L. Revesz, P. Hiestand, L. La Vecchia, R. Naef, H.-U. Naegeli, L. Oberer, and H.-J. Roth, Bioorg. Med. Chem. Lett., 9, 1521 (1999).CrossRefGoogle Scholar
  15. 15.
    Do Thi Thu Huong, Tran Thi Thu Thuy, Tran Thi Hien, Nguyen Thanh Tra, Nguyen Quyet Tien, I. E. Smirnova, O. B. Kazakova, E. M. Minnibaeva, and G. A. Tolstikov, Chem. Nat. Compd., 49, 58 (2013).CrossRefGoogle Scholar
  16. 16.
    I. E. Smirnova, O. B. Kazakova, D. T. T. Huong, E. M. Minnibaeva, A. N. Lobov, and K. Yu. Suponitsky, Nat. Prod. Commun., 9, 1417 (2014).PubMedGoogle Scholar
  17. 17.
    M. C. Alley, D. A. Scudiero, P. A. Monks, M. L. Hursey, M. J. Czerwinski, D. L. Fine, B. J. Abbott, J. G. Mayo, R. H. Shoemaker, and M. R. Boyd, Cancer Res., 48 (3), 589 (1988).PubMedGoogle Scholar
  18. 18.
    M. R. Grever, S. A. Schepartz, and B. A. Chabner, Semin. Oncol., 19, 622 (1992).PubMedGoogle Scholar
  19. 19.
    M. R. Boyd and K. D. Paull, Drug Dev., 34, 91 (1995).CrossRefGoogle Scholar
  20. 20.
    R. H. Shoemaker, Nat. Rev. Cancer, 6, 813 (2006).CrossRefGoogle Scholar
  21. 21.
    L. Q. Tran and K. Q. Tran, J. Chem., 36, 8 (1998).Google Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • I. E. Smirnova
    • 1
    Email author
  • A. V. Petrova
    • 1
  • O. B. Kazakova
    • 1
  1. 1.Ufa Institute of Chemistry, Ufa Scientific CenterRussian Academy of SciencesUfaRussia

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