Russian Chemical Bulletin

, Volume 67, Issue 4, pp 688–693 | Cite as

Synthesis of steroid analogs of tubuloclustin, their cytotoxicity and effect on microtubules of A549 carcinoma cells

  • E. V. Nurieva
  • N. A. Zefirov
  • A. V. Mamaeva
  • B. Wobith
  • S. A. Kuznetsov
  • O. N. ZefirovaEmail author
Full Article


Synthesis of analogs of tubuloclustin (N-(7-adamant-2-yloxy-7-oxoheptanoyl)-N-deacetylcolchicine (1)) with the colchicine fragment replaced with 2-methoxyestradiol scaffold attached via phenolic hydroxy group was described. Esters 3a–c exhibit moderate cytotoxicity (EC50 = 5–6 μmol L–1) and exert a weak effect on the microtubule network in A549 human lung carcinoma cells similar to the clustering effect of tubuloclustin and its derivatives. Conjugates 6a–c and 7a–c with the phenolic ester bond are low stable and compounds 7a–c are inactive to the microtubules of A549 cells, while compounds 6a–c cause an unusual effect of curling of the microtubules.

Key words

2-methoxyestradiol adamantane colchicine tubuloclustin tubulin microtubule network cytotoxicity A549 lung carcinoma cells 


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  1. 1.
    O. N. Zefirova, H. Lemcke, M. Lantow, E. V. Nurieva, B. Wobith, G. E. Onishchenko, A. Hoenen, G. Griffiths, N. S. Zefirov, S. A. Kuznetsov, ChemBioChem, 2013, 14, 1444.CrossRefPubMedGoogle Scholar
  2. 2.
    O. N. Zefirova, E. V. Nurieva, Ya. S. Glazkova, N. A. Zefirov, A. V. Mamaeva, B. Wobith, V. I. Romanenko, N. A. Lesnaya, E. M. Treshchalina, S. A. Kuznetsov, Pharm. Chem. J., 2014, 48,373.CrossRefGoogle Scholar
  3. 3.
    B. Kumar, R. Kumar, I. Skvortsova, V. Kumar, Curr. Cancer Drug Targets, 2017, 4,357.CrossRefGoogle Scholar
  4. 4.
    O. N. Zefirova, E. V. Nurieva, B. Wobith, V. V. Gogol, N. A. Zefirov, A. V. Ogonkov, D. V. Shishov, N. S. Zefirov, S. A. Kuznetsov, Mol. Divers., 2017, 21,547.CrossRefPubMedGoogle Scholar
  5. 5.
    O. N. Zefirova, Ya. S. Glazkova, E. V. Nurieva, N. A. Zefirov, A. V. Mamaeva, B. Wobith, N. S. Zefirov, S. A. Kuznetsov, Russ. Chem. Bull., 2014, 63, 1126.CrossRefGoogle Scholar
  6. 6.
    E. V. Nurieva, N. A. Zefirov, N. S. Zefirov, S. A. Kuznetsov, O. N. Zefirova, Russ. Chem. Bull., 2017, 64, 2248.CrossRefGoogle Scholar
  7. 7.
    B. S. Kumar, D. S. Raghuvanshi, M. Hasanain, S. Alam, J. Sarkar, K. Mitra, F. Khan, A. S. Negi, Steroids, 2016, 110,9.CrossRefPubMedGoogle Scholar
  8. 8.
    S. Verenich, P. M. Gerk, Mol. Pharmaceutics, 2010, 7, 2030.CrossRefGoogle Scholar
  9. 9.
    T. L. Nguyen, C. McGrath, A. R. Hermone, J. C. Burnett, D. W. Zaharevitz, B. W. Day, P. Wirf, E. Hamel, R. Gussio, J. Med. Chem., 2005, 48, 6107.CrossRefPubMedGoogle Scholar
  10. 10.
    N. A. Zefirov, O. N. Zefirova, Russ. J. Org. Chem., 2015, 51, 1207.CrossRefGoogle Scholar
  11. 11.
    M. Rajabi, M. Lanfranchi, F. Campo, L. Panza, Synth. Commun., 2014, 44, 1149.CrossRefGoogle Scholar
  12. 12.
    J. Klimentova, P. Kosak, K. Vavrova, T. Holas, A. Hrabálek, Bioorg. Med. Chem., 2006, 14, 7681.CrossRefPubMedGoogle Scholar
  13. 13.
    L. S. Suwandi, G. E. Agoston, J. H. Shah, A. D. Hanson, X. H. Zhan, T. M. LaVallee, A. M. Treston, Bioorg. Med. Chem. Lett., 2009, 19, 6459.CrossRefPubMedGoogle Scholar
  14. 14.
    T. Mosmann, J. Immunol. Methods, 1983, 65,55.CrossRefPubMedGoogle Scholar
  15. 15.
    E. V. Nurieva, N. A. Zefirov, A. V. Mamaeva, Y. K. Grishin, S. A. Kuznetsov, O. N. Zefirova, Mendeleev Commun., 2017, 27, 240.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • E. V. Nurieva
    • 1
  • N. A. Zefirov
    • 1
    • 2
  • A. V. Mamaeva
    • 1
  • B. Wobith
    • 3
  • S. A. Kuznetsov
    • 3
  • O. N. Zefirova
    • 1
    • 2
    Email author
  1. 1.Department of ChemistryM. V. Lomonosov Moscow State UniversityMoscow, Russian FederationRussia
  2. 2.Institute of Physiologically Active CompoundsRussian Academy of SciencesChernogolovka, Moscow Region, Russian FederationRussia
  3. 3.Institute of Biological SciencesUniversity of RostockRostockGermany

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