Hydrazines in the Synthesis of Cytotoxic N-Aryl(alkyl)-N-(hexaoxazadispiroalkyl)amines


An efficient method has been developed for the synthesis of N-aryl(alkyl)-N-(hexaoxazadispiroalkanyl)amines by the reaction of 3,6-di(spiroalkanyl)-substituted heptaoxacycloundecanes with hydrazine derivatives (3-chlorophenylhydrazine, phenylhydrazine, 2,4-dinitrophenylhydrazine, and tert-butylhydrazine) with Sm-containing catalysts. It was found that amines with macrocyclic spiro-linked azatriperoxide substituents exhibit a high cytotoxic activity against Jurkat, K562, and U937 tumor cell line and normal fibroblast cell line.

This is a preview of subscription content, log in to check access.



  1. 1

    Adam, W. and Forschungsgemeinschaft, D., Peroxides Chemistry: Mechanistic and Preparative Aspects of Oxygen Transfer, Weinheim: Wiley-VCH, 2000.

  2. 2

    Ando, W., Organic Peroxides, New York: Wiley, 1992.

  3. 3

    Jones, C.W., Applications of Hidrogen Peroxides and Derivatives, Cambridge: Royal Society of Chemistry, 1999.

  4. 4

    Chaturvedi, D., Goswami, A., Saikia, P.P., Barua, N.C., and Rao, P.G., Chem. Soc. Rev., 2010, vol. 39, p. 435. https://doi.org/10.1039/b816679j

    CAS  Article  PubMed  Google Scholar 

  5. 5

    O’Brien, C., Henrich, P.P., Passi, N., and Fidlock, D., Curr. Opin. Infect.Dis., 2011, vol. 24, p. 570. https://doi.org/10.1097/QCO.0b013e32834cd3ed

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  6. 6

    Slack, R.D., Jacobine, A.M., and Posner, G.H., Med.Chem. Commun., 2012, vol. 3, p. 281. https://doi.org/10.1039/C2MD00277A

    CAS  Article  Google Scholar 

  7. 7

    Ansari, M.T., Saify, Z.S., Sultana, N., Ahmed, I., Saeedul-Hassan, S., Tariq, I., and Khanum, M., Mini Rev. Med.Chem., 2013, vol. 13, p. 1879. https://doi.org/10.2174/13895575113136660097

    CAS  Article  PubMed  Google Scholar 

  8. 8

    Ariey, F., Witkowski, B., Amaratunga, C., Beghain, J., Langlois, A.-C., Khim, N., Kim, S., Duru, V., Bouchier, C., Ma, L., Lim, P., Leang, R., Duong, S., Sreng, S., Suon, S., Chuor, C.M., Bout, D.M., Menard, S., Rogers, W.O., Genton, B., Fandeur, T., Miotto, O., Ringwald, P., Le Bras, J., Berry, A., Barale, J.-C., Fairhurst, R.M., Benoit-Vical, F., Mercereau-Puijalon, O., and Menard, D., Nature, 2014, vol. 505, p. 50. https://doi.org/10.1038/nature12876

    CAS  Article  PubMed  Google Scholar 

  9. 9

    Makhmudiyarova, N.N., Ishmukhametova, I.R., Tyumkina, T.V., Ibragimov, A.G., and Dzhemilev, U.M., Tetrahedron Lett., 2018, vol. 59, p. 3161. https://doi.org/10.1016/j.tetlet.2018.07.010

    CAS  Article  Google Scholar 

  10. 10

    Makhmudiyarova, N.N., Ishmukhametova, I.R., Dzhemileva, L.U., Tyumkina, T.V., D’yakonov, V.A., Ibragimov, A.G., and Dzhemilev, U.M., RSC Adv., 2019, vol. 9, p. 18923. https://doi.org/10.1039/C9RA02950H

    CAS  Article  Google Scholar 

  11. 11

    Makhmudiyarova, N.N., Rakhimov, R.Sh., Tyumkina, T.V., Meshcheryakova, E.S., Ibragimov, A.G., and Dzhemilev, U.M., Russ. J. Org. Chem., 2019, vol. 55, p. 620. https://doi.org/10.1134/S1070428019050075

    CAS  Article  Google Scholar 

  12. 12

    Makhmudiyarova, N.N., Khatmullina, G.M., Rakhimov, R.Sh., Meshcheryakova, E.S., Ibragimov, A.G., and Dzhemilev, U.M., Tetrahedron, 2016, vol. 72, p. 3277. https://doi.org/10.1016/j.tet.2016.04.055

    CAS  Article  Google Scholar 

  13. 13

    Tyumkina, T.V., Makhmudiyarova, N.N., Kiyamutdinova, G.M., Meshcheryakova, E.S., Bikmukhametov, K.Sh., Abdullin, M.F., Khalilov, L.M., Ibragimov, A.G., and Dzhemilev, U.M., Tetrahedron, 2018, vol. 74, p. 1749. https://doi.org/10.1016/j.tet.2018.01.045

    CAS  Article  Google Scholar 

  14. 14

    Kukushkin, Yu.N., Reaktsionnaya sposobnost’ koordinatsionnykh soedinenii (Reactivity of Coordination Compounds), Leningrad: Khimiya, 1987.

  15. 15

    Pirson, R.D., Usp. Khim., 1971, vol. 40, p. 1259.

    Google Scholar 

  16. 16

    Denekamp, C., Gottlieb, L., Tamiri, T., Tsoglin, A., Shilav, R., and Karon, M., Org. Lett., 2005, vol. 7, p. 2461. https://doi.org/10.1021/ol050801c

    CAS  Article  PubMed  Google Scholar 

  17. 17

    Haroune, N., Crowson, A., and Campbell, B., Sci. Justice, 2011, vol. 56, p. 5150.

    Google Scholar 

  18. 18

    Terent’ev, A.O., Platonov, M.M., Sonneveld, E.J., Peschar, R., Chernyshev, V.V., Starikova, Z.A., and Nikishin, G.I., J. Org. Chem., 2007, vol. 72, p. 7237. https://doi.org/10.1021/jo071072c

    CAS  Article  PubMed  Google Scholar 

  19. 19

    Cherkasova, E.I. and Brilkina, A.A., Rabota s kulturami kletok (Work with Cell Cultures), Nizny Novgorod: Nizhegorod. Univ., 2015.

Download references


Cytotoxicity testing was performed at the Laboratory of Biological Screening and Molecular Design at the IPC RAS. The structural study was performed at the “Agidel” Center for Collective Use at the IPC RAS.


The work was financially supported by the Russian Science Foundation (project no. 18-73-00014).

Author information



Corresponding author

Correspondence to N. N. Makhmudiyarova.

Ethics declarations

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Makhmudiyarova, N.N., Ishmukhametova, I.R., Dzhemileva, L.U. et al. Hydrazines in the Synthesis of Cytotoxic N-Aryl(alkyl)-N-(hexaoxazadispiroalkyl)amines. Russ J Org Chem 56, 797–801 (2020). https://doi.org/10.1134/S1070428020050115

Download citation


  • catalysis
  • recycling
  • substituted hydrazines
  • heptaoxadispiroalkanes
  • N-aryl(alkyl)-N-(hexaoxazadispiroalkanyl)amines