Russian Chemical Bulletin

, Volume 68, Issue 1, pp 158–162 | Cite as

Hetarylfuroxans: cytotoxic effect and induction of apoptosis in chronic myeloid leukemia K562 cells

  • S. A. Pukhov
  • L. A. Anikina
  • A. A. Larin
  • L. L. Fershtat
  • A. S. Kulikov
  • N. N. MakhovaEmail author
Full Articles


Hetarylfuroxans (4-(2-methylpyridin-5-yloxy)-3-phenylfuroxan (1), bis(1,2,4-oxadiazol- 3-yl)furoxan (2), and 4-amino-3-(indenotriazin-3-yl)furoxan (3)) exhibit in vitro cytotoxic activity against chronic myeloid leukemia K562 cells. All studied furoxans induce apoptosis in K562 cells. The experiments with activation of caspases-3 and -7 showed that furoxan 3 possessed the highest apoptosis-inducing capacity. The studied hetarylfuroxans were found to be the promising drug candidates for the treatment of chronic myeloid leukemia K562.

Key words

cytotoxicity chronic myeloid leukemia K562 hetarylfuroxans apoptosis caspase-3 caspase-7 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    D. J. L. Joske, Med. J. Aust., 2008, 189, 277.Google Scholar
  2. 2.
    C.G. Geary, Br. J. Haematol., 2000, 110, 2.CrossRefGoogle Scholar
  3. 3.
    B. J. Druker, C. L. Sawyers, H. Kantarjian, D. J. Resta, S. F. Reese, J. M. Ford, R. Capdeville, M. Talpaz, N. Engl. J. Med., 2001, 344, 1038.CrossRefGoogle Scholar
  4. 4.
    E. Jabbour, H. Kantarjian, Am. J. Hematol., 2016, 91, 252.CrossRefGoogle Scholar
  5. 5.
    B. H. Moreno, E. C. Garralda, R. Hitt, Clin. Transl. Oncol., 2010, 12, 468.CrossRefGoogle Scholar
  6. 6.
    L. D. Azevedo, M. M. Bastos, F. C. Vasconcelos, L. V. B. Hoelz, F. P. S. Junior, R. F. Dantas, A. C. M. de Almeida, A. P. de Oliveira, L. C. Gomes, R. C. Maia, N. Boechat, Med. Chem. Res., 2017, 26, 2929.CrossRefGoogle Scholar
  7. 7.
    G. Rosti, F. Castagnetti, G. Gugliotta, F. Palandri, M. Baccarani, Cancer Treat. Rev., 2012, 38, 241.CrossRefGoogle Scholar
  8. 8.
    R. Cheng, L. A. Ridnour, S. A. Glynn, C. H. Switzer, W. Flores-Santana, P. Hussain, D. D. Thomas, S. Ambs, C. C. Harris, D. A. Wink, in Nitric Oxide and Cancer. Prognosis, Prevention and Therapy, Ed. B. Bonavida, Springer, New York, 2010, Chapter 1, p. 3.Google Scholar
  9. 9.
    M. R. Miller, I. L. Megson, Br. J. Pharmacol., 2007, 151, 305.CrossRefGoogle Scholar
  10. 10.
    N. N. Makhova, L. L. Fershtat, Tetrahedron Lett., 2018, 59, 2317.CrossRefGoogle Scholar
  11. 11.
    A. Gasco, K. Schoenafinger, in Nitric Oxide Donors: For Pharmaceutical and Biological Applications, Eds P. G. Wang, T. B. Cai, N. Taniguchi, Wiley-VCH, Weinheim, 2005, p. 131.Google Scholar
  12. 12.
    L. L. Fershtat, N. N. Makhova, Russ. Chem. Rev., 2016, 85, 1097.CrossRefGoogle Scholar
  13. 13.
    L. L. Fershtat, N. N. Makhova, ChemMedChem, 2017, 12, 622.CrossRefGoogle Scholar
  14. 14.
    T. Schiefer, L. VandeVrede, M. Fa, O. Arancio, G. R. J. Thatcher, J. Med. Chem., 2012, 55, 3076.CrossRefGoogle Scholar
  15. 15.
    J. L. Dos Santos, C. Lanaro, R. C. Chelucci, S. Gambero, P. L. Bosquesi, J. S. Reis, L. M. Lima, H. Cerecetto, M. Gonzalez, F. F. Costa, M. C. Chung, J. Med. Chem., 2012, 55, 7583.CrossRefGoogle Scholar
  16. 16.
    N. E. Ustyuzhanina, L. L. Fershtat, M. L. Gening, N. E. Nifantiev, N. N. Makhova, Mendeleev Commun., 2016, 26, 513.CrossRefGoogle Scholar
  17. 17.
    N. E. Ustyuzhanina, L. L. Fershtat, M. L. Gening, N. E. Nifantiev, N. N. Makhova, Mendeleev Commun., 2018, 28, 49.CrossRefGoogle Scholar
  18. 18.
    S. G. Zlotin, A. M. Churakov, I. L. Dalinger, O. A. Luk´yanov, N. N. Makhova, A. Yu. Sukhorukov, V. A. Tartakovsky, Mendeleev Commun., 2017, 27, 535.CrossRefGoogle Scholar
  19. 19.
    A. S. Kulikov, M. A. Epishina, A. I. Churakov, L. V. Anikina, L. L. Fershtat, N. N. Makhova, Mendeleev Commun., 2018, 28, 623.CrossRefGoogle Scholar
  20. 20.
    A. A. Larin, L. L. Fershtat, N. E. Ustyuzhanina, M. L. Gening, N. E. Nifantiev, N. N. Makhova, Mendeleev Commun., 2018, 28, 595.CrossRefGoogle Scholar
  21. 21.
    H. Cerecetto, W. Porcal, Mini-Rev. Med. Chem., 2005, 5, 57.CrossRefGoogle Scholar
  22. 22.
    A. S. Kulikov, A. A. Larin, L. L. Fershtat, L. V. Anikina, S. A. Pukhov, S. G. Klochkov, M. I. Struchkova, A. A. Romanova, I. V. Ananyev, N. N. Makhova, Arkivoc, 2017, Part III, 250.Google Scholar
  23. 23.
    L. L. Fershtat, M. A. Epishina, A. S. Kulikov, M. I. Struchkova, N. N. Makhova, Chem. Heterocycl. Compd., 2015, 51, 176.CrossRefGoogle Scholar
  24. 24.
    L. L. Fershtat, I. V. Ananyev, N. N. Makhova, RSC Adv., 2015, 5, 47248.CrossRefGoogle Scholar
  25. 25.
    L. L. Fershtat, A. A. Larin, M. A. Epishina, I. V. Ovchinnikov, A. S. Kulikov, I. V. Ananyev, N. N. Makhova, RSC Adv., 2016, 6, 31526.CrossRefGoogle Scholar
  26. 26.
    A. Ashkenazi, V. M. Dixit, Science, 1998, 281, 1305.CrossRefGoogle Scholar
  27. 27.
    H. Steller, Science, 1995, 267, 1445.CrossRefGoogle Scholar
  28. 28.
    D. M. Pereira, G. Correia-da-Silva, P. Valentão, N. Teixeira, P. B. Andrade, Mar. Drugs, 2014, 12, 54.CrossRefGoogle Scholar
  29. 29.
    E. A. Slee, C. Adrain, S. J. Martin, Cell Death Diff., 1999, 6, 1067.CrossRefGoogle Scholar
  30. 30.
    N. A. Thornberry, T. A. Rano, E. P. Peterson, D. M. Rasper, T. Timkey, M. Garcia-Calvo, V. M. Houtzager, P. A. Nordstrom, S. Roy, J. P. Vaillancourt, K. T. Chapman, D. W. Nicholson, J. Biol. Chem., 1997, 272, 17907.CrossRefGoogle Scholar
  31. 31.
    J. O´Brien, I. Wilson, T. Orton, F. Pognan, Eur. J. Biochem., 2000, 267, 5421.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2019

Authors and Affiliations

  • S. A. Pukhov
    • 1
  • L. A. Anikina
    • 1
  • A. A. Larin
    • 2
  • L. L. Fershtat
    • 2
  • A. S. Kulikov
    • 2
  • N. N. Makhova
    • 2
    Email author
  1. 1.Institute of Physiologically Active CompoundsRussian Academy of SciencesChernogolovka, Moscow RegionRussian Federation
  2. 2.N. D. Zelinsky Institute of Organic ChemistryRussian Academy of SciencesMoscowRussian Federation

Personalised recommendations