Screening of potential substrates or inhibitors of cytochrome P450 17A1 (CYP17A1) by electrochemical methods

  • V. V. Shumyantseva
  • T. V. Bulko
  • A. Yu. Misharin
  • A. I. Archakov


The electrochemical redox reactions of the recombinant form of human cytochrome P450 17A1 (CYP17A1) were investigated. The hemoprotein was immobilized on the electrode modified with a biocompatible nanocomposite material based on the membrane-like synthetic surfactant didodecyldimethylammonium bromide (DDAB) and gold nanoparticles. Analytical characteristics of DDAB/Au/CYP17A1 electrodes were investigated using cyclic voltammetry, square wave voltammetry, and differential pulse voltammetry. Analysis of electrochemical behavior of cytochrome P450 17A1 was performed in the presence of a natural substrate, pregnenolone (1), known inhibitor, ketoconazole (2), and in the presence of synthetic derivatives of pregnenolone: acetyl pregnenolone (3), cyclopregnenolone (4), and tetrabromo-pregnenolone (5). Ketoconazole, the azole inhibitor of cytochromes P450, blocked catalytic current in the presence of the substrate, pregnenolone (1). Compounds 3–5 did not demonstrate substrate properties towards the electrode/CYP17A1 system. Compound 3 did not influence catalytic activity with pregnenolone, whereas compounds 4 and 5 demonstrated some inhibitory activity. Thus, electrochemical redox reactions of CYP17A1 may serve as an adequate substitution of the reconstituted system, which requires additional redox partners for manifestation of catalytic activity of hemoproteins of the cytochrome P450 superfamily.


recombinant form of human cytochrome P450 17A1 electrochemistry inhibitors pregnenolone 


  1. 1.
    Archakov, A.I. and Bachmanova, G.I., Cytochrome P450 and Active Oxygen, London: Taylor and Francis, 1990.Google Scholar
  2. 2.
    Lewis, D.F.V., Ed., Guide to Cytochrome P450. Structure and Function, London and New York: Taylor and Francis, 2001.Google Scholar
  3. 3.
    Yap, T.A., Carden, C.P., Attard, G., de Bono, J.S., Curr. Opin. Pharmacol., 2008, vol. 8, pp. 449–457.CrossRefGoogle Scholar
  4. 4.
    Madigan, M.P., Gao, Y.T., Deng, J., Pfeiffer, R.M., Chang, B.L., Zheng, S., et al., Int. J. Cancer, 2003, vol. 107, pp. 271–275.CrossRefGoogle Scholar
  5. 5.
    Hakki, T. and Bernhardt, R., Pharmacology & Therapeutics, 2006, vol. 111, pp. 27–52.CrossRefGoogle Scholar
  6. 6.
    Li, J.S., Li, Y., Son, C., and Brodie, A.M., J. Med. Chem., 1996, vol. 39, pp. 4335–4339.CrossRefGoogle Scholar
  7. 7.
    Handratta, V.D., Vasaitis, T.S., Njar, V.C., Gediya, L.K., Kataria, R., Chopra, P., et al., J. Med. Chem., 2005, vol. 48, pp. 2972–2984.CrossRefGoogle Scholar
  8. 8.
    Hutschenreuter, T.U., Ehmer, P.B., and Hartmann, R.W., J. Enzyme Inhib. Med. Chem., 2004, vol. 19, pp. 17–32.CrossRefGoogle Scholar
  9. 9.
    Duc., I., Duranti, V., Cardinali, S., Riviete, A., De Giovanni, A., Shieda-Botelle, J., Barcelo, G., Adje, N., Carniato, D., Lafay, J., Pascal, J.C., and Delansorne, R., J. Steroid Biochem. Mol. Biol., 2003, vol. 84, pp. 537–542.Google Scholar
  10. 10.
    Jagusch, C., Negri, M., Hille, U., Hu, Q., Bartels, M., Jahn-Hoffmann, K., Mendieta, M., Rodenwaidt, B., Muller-Vieira, U., Schmidt, D., Lauterbach, Th., Recantini, M., Cavalli, A., and Hartmann, R., Bioorg. Med. Chem., 2008, vol. 16, pp. 1992–2010.CrossRefGoogle Scholar
  11. 11.
    Mendieta, M., Negri, M., Jagusch, C., Hille, U., Muller-Viera, U., Schmidt, D., Hansen, K., and Hartmann, R., Bioorg. Med. Chem. Lett., 2008, vol. 18, pp. 267–273.CrossRefGoogle Scholar
  12. 12.
    Bruno, R.D. and Njar, C.O., Bioorg. Med. Chem., 2007, vol. 15, pp. 5047–5060.CrossRefGoogle Scholar
  13. 13.
    Bruttomesso, A.C., Eiras, J., Ramirez, J., and Galagovsky, L.R., Tetraherdon Lett., 2009, vol. 50, pp. 4022–4024.CrossRefGoogle Scholar
  14. 14.
    Haidar, S., Ehmer, P., Barassin, S., Batzl-Hartmann, C., and Hartmann, R.W., J. Steroid Biochem. Mol. Biol., 2003, vol. 84, pp. 555–562.Google Scholar
  15. 15.
    Shumyantseva, V.V., Bulko, T.V, Rudakov, Yu.O., Kuznetsova, G.P., Samenkova, N.F., Lisitsa, A.V., Karuzina, I.I, and Archakov, A.I., J. Inorg. Biochem., 2007, vol. 101, pp. 859–865.CrossRefGoogle Scholar
  16. 16.
    Bistolas, N., Wollenberger, U., Jung, C., and Scheller, F.W., Biosens. Bioelectron., 2005, vol. 20, pp. 2408–2423.CrossRefGoogle Scholar
  17. 17.
    Shumyantseva, V.V., Bulko, T.V., and Archakov, A.I., J. Inorg. Biochem., 2005, vol. 99, pp. 1051–1063.CrossRefGoogle Scholar
  18. 18.
    Udit, A.K. and Gray, H.B., Biochem. Biophys. Res. Commun., 2005, vol. 338, pp. 470–476.CrossRefGoogle Scholar
  19. 19.
    Jonson, D.L., Conley, A.J., and Martin, L.L., J. Mol. Endocrinol., 2006, vol. 36, pp. 349–359.CrossRefGoogle Scholar
  20. 20.
    Julian, P.L. and Karpel, W.J., J. Am. Chem. Soc., 1950, vol. 72, pp. 362–366.CrossRefGoogle Scholar
  21. 21.
    Partridge, J.J., Faber, S., and Uskokovic, M.R., Helv. Chim. Acta, 1974, vol. 57, p. 764.Google Scholar
  22. 22.
    Shumyantseva, V.V., Bulko, T.V., Kuznetsova, G.P., Samenkova, N.F., and Archakov, A.I., Biochemistry (Moscow), 2009, vol. 74, pp. 438–444.CrossRefGoogle Scholar
  23. 23.
    Gooding, J.J., Electrochimica Acta, 2005, vol. 50, pp. 3049–3060.CrossRefGoogle Scholar
  24. 24.
    Broun, K.R., Fox, A.P., Natan, M.J., J. Am. Chem. Soc., 1996, vol. 118, pp. 1154–1157.CrossRefGoogle Scholar
  25. 25.
    Daniel, M.-Ch. and Astruc, D., Chem. Rev., 2004, vol. 104, pp. 293–346.CrossRefGoogle Scholar
  26. 26.
    Cheng, W., Dong, S., and Wang, E., Langmuir, 2002, vol. 18, pp. 9947–9952.CrossRefGoogle Scholar
  27. 27.
    Riley, D.J., Curr. Opin. Colloid Interface Sci., 2002, vol. 7, pp. 186–192.CrossRefGoogle Scholar
  28. 28.
    Broun, A.P., Koval, C., and Anson, F.C., J. Electroanal. Chem., 1976, vol. 72, pp. 379–387.CrossRefGoogle Scholar
  29. 29.
    Ferapontova, E.E., Ruzgas, T., and Gorton, L., Anal Chem., 2003, vol. 75, pp. 4841–4850.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • V. V. Shumyantseva
    • 1
  • T. V. Bulko
    • 1
  • A. Yu. Misharin
    • 1
  • A. I. Archakov
    • 1
  1. 1.Institute of Biomedical ChemistryRussian Academy of Medical SciencesMoscowRussia

Personalised recommendations