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Screening of human cytochrome P450(51) (CYP51A1) inhibitors: Structural lanosterol analogues of plant and animal origin

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Abstract

Inhibition of cholesterol biosynthesis at post-squalene steps provide the alternative to classic statin therapy. Sterol-14α-demethylase (CYP51) is one of potential targets for such inhibition. In this study screening of potential ligands of human CYP51 (CYP51A1) among natural low-weight compounds containing steroid-like moiety has been performed by means of integration of surface plasmon resonance and spectral titration methods. Four compounds (betulafolientriol, holothurin A, theasaponin, capsicosine) exhibited high affinity to the active site of CYP51A1. These data extend the known range of compounds, which may be used as specific inhibitors of CYP51.

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References

  1. Taylor, F., Ward, K., Moore, T.H., Burke, M., Davey Smith, G., Casas, J.P., and Ebrahim, S., Cochrane Database Syst Rev., 2011, vol. 1, CD004816. DOI: 10.1002/14651858.CD004816.pub4.

    Google Scholar 

  2. Baker, S.K., Muscle Nerve, 2005, vol. 31, pp. 572–580.

    Article  CAS  Google Scholar 

  3. Korošec, T., Ačimovič, J., Seliškar, M., Kocjan, D., Fon Tacer, K., Rozman, D., and Urleb, U., Bioorg. Med. Chem., 2008, vol. 16, pp. 209–221.

    Article  Google Scholar 

  4. Lamb, D.C., Kelly, D.E., and Kelly, S.L., FEBS Lett., 1998, vol. 425, pp. 263–265.

    Article  CAS  Google Scholar 

  5. Nagai, K., Miyamori, I., Takeda, R., Suhara, K., and Katagiri, M., J. Steroid Biochem., 1987, vol. 28, pp. 333–336.

    Article  CAS  Google Scholar 

  6. Kragie, L., Turner, S.D., Patten, C.J., Crespi, C.L., and Stresser, D.M., Endocr. Res., 2002, vol. 28, pp. 129–140.

    Article  CAS  Google Scholar 

  7. Giavini, E. and Menegola, E., Toxicol Lett., 2010, vol. 198, pp. 106–111. DOI: 10.1016/j.toxlet.2010.07.005.

    Article  CAS  Google Scholar 

  8. Trzaskos, J.M., Magolda, R.L., Favata, M.F., Fischer, R.T., Johnson, P.R., Chen, H.W., Ko, S.S., Leonard, D.A., and Gaylor, J.L., J. Biol. Chem., 1993, vol. 268, pp. 22591–22599.

    CAS  Google Scholar 

  9. Trzaskos, J.M., Ko, S.S., Magolda, R.L., Favata, M.F., Fischer, R.T., Stam, S.H., Johnson, P.R., and Gaylor, J.L., Biochemistry, 1995, vol. 34, pp. 9670–9676.

    Article  CAS  Google Scholar 

  10. Cooper, A.B., Wright, J.J., Ganguly, A.K., Desai, J., Loebenberg, D., Parmegiani, R., and Feingold, D.S. Ann. N.Y. Acad. Sci., 1988, vol. 544, pp. 109–112.

    Article  CAS  Google Scholar 

  11. Frye, L.L., Cusack, K.P., and Leonard, D.A., J. Med. Chem., 1993, vol. 36, pp. 410–416.

    Article  CAS  Google Scholar 

  12. Frye, L.L. and Robinson, C.H., J. Org. Chem., 1990, vol. 55, no. 5, pp. 1579–1584.

    Article  CAS  Google Scholar 

  13. Bossard, M.J., Tomaszek, T.A., Jr., Gallagher, T.F., Metcalf, B.W., and Adams, J.L., Bioorganic Chem., 1991, vol. 19, pp. 418–432.

    Article  CAS  Google Scholar 

  14. Strushkevich, N., Usanov, S.A., and Park, H.-W., J. Mol. Biol., 2010, vol. 397, pp. 1067–1078.

    Article  CAS  Google Scholar 

  15. Monk, B.C., Tomasiak, T. M., Keniya, M. V., Huschmann, F. U., Tyndall, J. D., O’Connell, J. D., Cannon, R.D., McDonald, J.G., Rodriguez, A., Finer-Moore, J. S., and Stroud, R.M., Proc. Natl. Acad. Sci. USA, 2014, vol. 111, pp. 3865–3870.

    Article  CAS  Google Scholar 

  16. Mukha, D.V., Feranchuk, S.I., Gilep, A.A., and Usanov, S.A., Biochemistry (Moscow), 2011, vol. 76, pp. 175–185.

    Article  CAS  Google Scholar 

  17. Gnedenko, O.V., Kaluzhskiy, L.A., Molnar, A.A., Yantsevich, A.V., Mukha, D.V., Gilep, A.A., Usanov, S.A., Stonik, V.A., Ivanov, A.S., Lisitsa, A.V., and Archakov, A.I., Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 2013, vol. 7, pp. 187–195.

    Article  Google Scholar 

  18. Pilipenko, V.V., Sukhodub, L.F., Aksyonov, S.A., Kalinkevich, A.N., and Kintia, P.K., Rapid. Commun. Mass. Spectrom., 2000, vol. 14, pp. 819–823.

    Article  CAS  Google Scholar 

  19. Dimoglo, A.S., Choban, I.N., Bersuker, I.B., Kintya, P.K., and Balashova, N.N., Bioorgan. Khim., 1985, vol. 11, pp. 408–413.

    CAS  Google Scholar 

  20. Ershov, P.V., Gnedenko, O.V., Molnar, A.A., Lisitsa, A.V., Ivanov, A.S., and Archakov, A.I., Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 2009, vol. 3, pp. 272–288.

    Article  Google Scholar 

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Authors and Affiliations

  1. Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences, ul. Pogodinskaya 10, Moscow, 119121, Russia

    L. A. Kaluzhskiy, O. V. Gnedenko, A. S. Ivanov, A. V. Lisitsa & A. I. Archakov

  2. Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, Minsk, Belarus

    A. A. Gilep, N. V. Strushkevich, T. V. Shkel & A. S. Usanov

  3. National Research Center for Pediatric Oncology, Hematology and Immunology, Minsk region, Borovlyany, Belarus

    M. A. Chernovetsky

  4. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Vladivostok, Russia

    V. A. Stonik

Authors
  1. L. A. Kaluzhskiy
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  2. O. V. Gnedenko
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  3. A. A. Gilep
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  4. N. V. Strushkevich
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  5. T. V. Shkel
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  6. M. A. Chernovetsky
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  7. A. S. Ivanov
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  8. A. V. Lisitsa
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  9. A. S. Usanov
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  10. V. A. Stonik
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  11. A. I. Archakov
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Corresponding author

Correspondence to L. A. Kaluzhskiy.

Additional information

Original Russian Text © L.A. Kaluzhskiy, O.V. Gnedenko, A.A. Gilep, N.V. Strushkevich, T.V. Shkel, M.A. Chernovetsky, A.S. Ivanov, A.V. Lisitsa, A.S. Usanov, V.A. Stonik, A.I. Archakov, 2014, published in Biomeditsinskaya Khimiya.

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Kaluzhskiy, L.A., Gnedenko, O.V., Gilep, A.A. et al. Screening of human cytochrome P450(51) (CYP51A1) inhibitors: Structural lanosterol analogues of plant and animal origin. Biochem. Moscow Suppl. Ser. B 8, 349–360 (2014). https://doi.org/10.1134/S199075081404012X

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  • DOI: https://doi.org/10.1134/S199075081404012X

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