Russian Chemical Bulletin

, Volume 63, Issue 5, pp 1181–1186 | Cite as

New 3,5-bis(arylidene)-4-piperidones with bisphosphonate moiety: synthesis and antitumor activity

  • M. V. Makarov
  • E. Yu. Rybalkina
  • G. -V. Röschenthaler
Full Articles


An approach to the synthesis of new conjugates of 3,5-bis(arylidene)-4-piperidone pharmacophore with bisphosphonate moiety separated from the nitrogen atom of piperidone ring by four methylene units has been developed. This approach is based on the reaction of tetraethyl vinylidene-1,1-bisphosphonate with the Grignard reagent containing a dioxolane-protected piperidone ring (4-piperidone ethylene ketal), which is followed by the crotonic condensation of bisphosphonate obtained with aromatic aldehydes. In vitro evaluation of antitumor activity of prepared conjugates 3a,b toward human cancer cell lines Caov3, Scov3, KB3-1, KB8-5, A549, and MCF7 has revealed that these compounds possess moderate antitumor activity and are inferior in cytotoxicity to the analogs 1a,b with one methylene unit between piperidone and bisphosphonate moieties.

Key words

3,5-bis(arylidene)-4-piperidones bisphosphonates aminobisphosphonates antitumor activity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    U. Das, R. K. Sharma, J. R. Dimmock, Curr. Med. Chem., 2009, 16, 2001.CrossRefGoogle Scholar
  2. 2.
    M. Gregory, A. Dandavati, M. Lee, S. Tzou, M. Savagian, K. A. Brien, V. Satam, P. Patil, M. Lee, Med. Chem. Res., 2013, 22, 5588.CrossRefGoogle Scholar
  3. 3.
    T. K’alai, M. L. Kuppusamy, M. Balog, K. Selvendiran, B. K. Rivera, P. Kuppusamy, K. Hideg, J. Med. Chem., 2011, 54, 5414.CrossRefGoogle Scholar
  4. 4.
    S. Das, U. Das, D. Michel, D. K. J. Gorecki, J. R. Dimmock, Eur. J. Med. Chem., 2013, 64, 321.CrossRefGoogle Scholar
  5. 5.
    M. V. Makarov, E. S. Leonova, E. Yu. Rybalkina, V. N. Khrustalev, N. E. Shepel, G.-V. Röschenthaler, T. V. Timofeeva, I. L. Odinets, Arch. Pharm. Chem. Life Sci., 2012, 345, 349.CrossRefGoogle Scholar
  6. 6.
    F. R. Quinn, G. W. A. Milne, Fundam. Appl. Toxicol., 1986, 6, 270.CrossRefGoogle Scholar
  7. 7.
    M. V. Makarov, E. S. Leonova, E. Yu. Rybalkina, P. Tongwa, V. N. Khrustalev, T. V. Timofeeva, I. L. Odinets, Eur. J. Med. Chem., 2010, 45, 992.CrossRefGoogle Scholar
  8. 8.
    E. S. Leonova, M. V. Makarov, E. Yu. Rybalkina, S. L. Nayani, P. Tongwa, A. Fonari, T. V. Timofeeva, I. L. Odinets, Eur. J. Med. Chem., 2010, 45, 5926.CrossRefGoogle Scholar
  9. 9.
    A. E. Shipov, M. V. Makarov, P. V. Petrovskii, E. Yu. Rybalkina, Yu. V. Nelyubina, I. L. Odinets, Heteroatom Chem., 2013, 24, 191.CrossRefGoogle Scholar
  10. 10.
    M. V. Makarov, E. Yu. Rybalkina, G.-V. Röschenthaler, K. W. Short, T. V. Timofeeva, I. L. Odinets, Eur. J. Med. Chem., 2009, 44, 2135.CrossRefGoogle Scholar
  11. 11.
    R. G. G. Russell, Phosphorus, Sulfur, Silicon, Relat. Elem. 1999, 144–146, 793.Google Scholar
  12. 12.
    K. Stach, M. Thiel, F. Bickelhaupt, Monatshefte für Chemie, 1962, 93, 1090.CrossRefGoogle Scholar
  13. 13.
    M. L. Lolli, L. Lazzarato, A. Di Stilo, R. Fruttero, A. Gasco, J. Organomet. Chem., 2002, 650, 77.CrossRefGoogle Scholar
  14. 14.
    J. van Meerloo, G. J. L. Kaspers, J. Cloos, in Methods in Molecular Biology, Ed. I. A. Cree, Humana Press, 2011, 731, 502.Google Scholar
  15. 15.
    C. R. Degenhardt, D. C. Burdsall, J. Org. Chem., 1986, 51, 3488.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • M. V. Makarov
    • 1
  • E. Yu. Rybalkina
    • 2
  • G. -V. Röschenthaler
    • 3
  1. 1.A. N. Nesmeyanov Institute of Organoelement CompoundsRussian Academy of SciencesMoscowRussian Federation
  2. 2.Institute of Carcinogenesis of the N. N. Blokhin Russian Cancer Scientific CenterRussian Academy of Medical SciencesMoscowRussian Federation
  3. 3.Jacobs UniversityBremenGermany

Personalised recommendations