Russian Chemical Bulletin

, Volume 67, Issue 4, pp 700–704 | Cite as

Sulfur-containing phenolic antioxidants increasing antitumor efficiency of cyclophosphamide and its combination with nitric oxide donor

  • T. N. BogatyrenkoEmail author
  • N. V. Kandalintseva
  • T. E. Sashenkova
  • D. V. Mishchenko
Full Article


Due to the multifactorial nature of cancer diseases, investigations of combinations of the known cytostatics with substances that are chemosensitizers and act on various molecular target in the organism gain increasing significance. Polyfunctional compounds, whose molecules contain several reaction centers, serve as resources improving the efficiency of the chemosensitizing effect of various substances for chemotherapy by cytostatic agents. Classical representatives of such polyfunctional substances are sulfur-containing derivatives of alkylated phenols, the high oxidation activity of which is determined by a combination of the antiradical activity of the phenol fragments with the antiperoxide activity of the sulfur-containing groups. It is shown that the sulfur-containing phenolic antioxidant sodium S-[3-(3-tert-butyl-4-hydroxyphenyl) propyl] thiosulfate (TC-13) has no antitumor activity but enhances chemotherapeutic activity of cytostatic cyclophosphamide taken in a subtherapeutic dose, increasing the index of average life span of mice with leukemia P388 from 196 to 283%. In addition, a combination of TC-13 with the nitric oxide donor (NaNO2) increases the antitumor activity of cytostatic cyclophosphamide by 110% for the same experimental model of mice at 50% survived animals.

Key words

cyclophosphamide sulfur-containing phenolic antioxidants nitric oxide lympho cytic leukemia P388 inflammation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    H. F. Dvorak, New Engl. J. Med., 1986, 315, 1650.CrossRefPubMedGoogle Scholar
  2. 2.
    I. A. Kudryavtsev, N. V. Maysishcheva, Ros. Bioterapevt. Zh. [Russ. Biotherapeut. J.], 2008, 7, No. 3, 48 (in Russian).Google Scholar
  3. 3.
    T. N. Bogatyrenko, N. P. Konovalova, A. M. Sipyagin, V. R. Bogatyrenko, Z. V. Kuropteva, L. M. Baider, T. E. Sashenkova, B. S. Fedorov, Russ. Chem. Bull., 2014, 63, 1187.CrossRefGoogle Scholar
  4. 4.
    T. N. Bogatyrenko, Z. V. Kuropteva, L. M. Baider, I. V. Serkov, V. R. Bogatyrenko, T. E. Sashenkova, E. N. Klimanova, D. V. Michenko, N. P. Konovalova, Russ. Chem. Bull., 2016, 65, 2509.CrossRefGoogle Scholar
  5. 5.
    S. W. Rowlison, C. Grews, D. C. Gudwin, J. Biol. Chem., 2000, 275, 9, 6589.CrossRefGoogle Scholar
  6. 6.
    J. Mathers, J. A. Fraser, M. McMahon, Biochem. Soc. Symp., 2004, 71,157.CrossRefGoogle Scholar
  7. 7.
    N. K. Klaan, T. A. Pronina, L. P. Akinshina, V. V. Reshetnikova, Ros. Bioterapevt. Zh. [Russ. Biotherapeut. J.], 2014, 13, No. 1, 3 (in Russian).Google Scholar
  8. 8.
    T. N. Bogatyrenko, Z. V. Kuropteva, L. M. Baider, T. E. Sashenkova, D. V. Michenko, V. R. Bogatyrenko, N. P. Konovalova, Russ. Chem. Bull., 2016, 65,561.CrossRefGoogle Scholar
  9. 9.
    E. B. Menshchikova, N. K. Zenkov, V. O. Tkachev, A. E. Lemza, N. V. Kandalintseva, Bull. Exp. Biol. Med., 2013, 155,330.CrossRefPubMedGoogle Scholar
  10. 10.
    E. B. Menshchikova, V. O. Tkachev, N. K. Zenkov, A. E. Lemza, T. V. Sharkova, N. V. Kandalintseva, Bull. Exp. Biol. Med., 2013, 155,366.CrossRefPubMedGoogle Scholar
  11. 11.
    A. E. Prosenko, S. Yu. Klepikova, N. V. Kandalintseva, O. I. Dyubchenko, M. I. Dushkin, N. K. Zenkov, E. B. Menshchikova, Byul. VSNTs SO RAMN [Bulletin of the East Siberian Scientific Center of the Siberian Division of the Russian Academy of Medical Sciences], 2001, No. 1, 114 (in Russian).Google Scholar
  12. 12.
    Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv [Manual on Preclinic Studies of Drugs], Ed. A. N. Mironov, Part 1, Grif i K, Moscow, 2012, 944 pp. (in Russian).Google Scholar
  13. 13.
    E. M. Treshchalina, O. S. Zhukova, G. K. Gerasimova, N. V. Andronova, A. M. Garin, Rukovodstvo po eksperi mental´nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv: metodicheskie ukazaniya izucheniyu protivoopukholevoi aktivnosti farmakologicheskikh veshchestv [Manual on Experimental (Preclinic) Study of New Pharmacological Substances: Methodical Instructions of Studying Antitumor Activity of Pharmacological Substances], Meditsina, Moscow, 2005, 637 pp. (in Russian).Google Scholar
  14. 14.
    Eksperimental´naya otsenka protivoopukholevykh preparatov v SSSR i SShA [Experimental Evaluation of Antitumor Drugs in the USSR and USA], Eds Z. P. Sof´ina, A. B. Syrkin, A. Goldin, A. Klein, Meditsina, Moscow, 1980, 293 pp. (in Russian).Google Scholar
  15. 15.
    D. B. Korman, Misheni i mekhanizmy deistviya protivoopukholevykh preparatov [Targets and Mechanisms of Antitumor Drugs], Prakticheskaya Meditsina, Moscow, 2014, 336 pp. (in Russian).Google Scholar
  16. 16.
    Z. V. Kuropteva, M. E. Kudriavstev, Biophysics (Moscow), 1997, 42,484.Google Scholar
  17. 17.
    R. N. Harris, P. J. Basseches, P. L. Appel, A. M. Durski, G. Powis, Cancer Chemother. Pharmacol., 1984, 12,164.CrossRefGoogle Scholar
  18. 18.
    V. P. Reutov, Biochemistry (Moscow), 2002, 67,293.CrossRefGoogle Scholar
  19. 19.
    O. V. Tkachev, E. B. Menshchikova, N. K. Zenkov, N. V. Kandalintseva, N. N. Vol´skii, Biochemistry (Moscow), 2010, 75, 549.CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • T. N. Bogatyrenko
    • 1
    Email author
  • N. V. Kandalintseva
    • 2
  • T. E. Sashenkova
    • 1
  • D. V. Mishchenko
    • 1
  1. 1.Institute of Problems of Chemical PhysicsRussian Academy of SciencesChernogolovka, Moscow Region, Russian FederationRussia
  2. 2.Novosibirsk State Pedagogical UniversityNovosibirsk, Russian FederationRussia

Personalised recommendations