Advertisement

Russian Chemical Bulletin

, Volume 67, Issue 4, pp 682–687 | Cite as

Oxazoline derivatives of [17(20)E]-21-norpregnene – inhibitors of CYP17A1 activity and proliferation of prostate carcinoma cells

  • V. A. Kostin
  • A. S. Latysheva
  • V. A. Zolottsev
  • Ya. V. Tkachev
  • V. P. Timofeev
  • A. V. Kuzikov
  • V. V. Shumyantseva
  • G. E. Morozevich
  • A. Yu. Misharin
Full Article
  • 21 Downloads

Abstract

Nine new oxazolinyl derivatives of [17(20)E]-21-norpregnene, differing in the structure of steroid moiety, were investigated for their potency to inhibit the CYP17A1 catalytic activity, as well as growth and proliferation of LNCaP and PC-3 prostate carcinoma cell lines. The activity of one of the investigated compounds, 2´-{[(E)3β-hydroxyandrost-5-en-17-ylidene]methyl}-4´,5´-dihydro-1´,3´-oxazole (1), was found to be comparable with that of Abiraterone, a known inhibitor of CYP17A1 used for treatment of prostate cancer. A model of the interaction of oxazoline 1 with the active site of CYP17A1 was constructed by the molecular dynamics method. A correlation was found between the structure and the biological activity in the series of [17(20)E]-21-norpregnene oxazolinyl derivatives.

Key words

steroids CYP17A1 inhibitors prostate carcinoma cells molecular dynamics structure–biological activity interrelation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Cytochrome P-450: structure, mechanism, and biochemistry, 3rd ed., Ed. P. R. Ortiz de Montellano, Kluwer Academic/Plenum Press, New York, 2005, 690 pp.Google Scholar
  2. 2.
    M. Akhtar, J. N. Wright, in Advances in Experimental Medicine and Biology 851, Eds. E. G. Hrycay, S. M. Bandiera, Springer, Cham–Heidelberg–New York–Dortrecht–London, 2015, p.107.Google Scholar
  3. 3.
    F. K. Yoshimoto, R. J. Auchus, J. Steroid Biochem. Mol. Biol., 2015, 151,52.CrossRefPubMedGoogle Scholar
  4. 4.
    A. B. Alex, S. K. Pal, N. Agarwal, Ther. Adv. Med. Oncol., 2016, 8,267.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    L. Gomez, J. R. Kovac, D. J. Lamb, Steroids, 2015, 95,80.CrossRefPubMedGoogle Scholar
  6. 6.
    R. D. Bruno, V. C. Njar, Bioorg. Med. Chem., 2007, 15, 5047.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    E. Baston, F. R. Leroux, Rec. Pat. Anticancer Drug Discov., 2007, 2,31.CrossRefGoogle Scholar
  8. 8.
    C. P. Owen, Anticancer Agents Med. Chem., 2009, 9,613.CrossRefPubMedGoogle Scholar
  9. 9.
    V. M. Moreira, J. A. Salvador, T. S. Vasaitis, V. C. Njar, Curr. Med. Chem., 2008, 15,868.CrossRefPubMedGoogle Scholar
  10. 10.
    J. A. Salvador, R. M. Pinto, S. M. Silvestre, J. Steroid Biochem. Mol. Biol., 2013, 137,199.CrossRefPubMedGoogle Scholar
  11. 11.
    J. A. Salvador, V. M. Moreira, S. M. Silvestre, in Steroidal CYP17 Inhibitors for Prostate Cancer Treatment: From Concept to Clinic. Advances in Prostate Cancer, Intech, 2013, p.275.Google Scholar
  12. 12.
    O. O. Clement, C. M. Freeman, R. W. Hartmann, V. D. Handratta, T. S. Vasaitis, A. M. Brodie, V. C. Njar, J. Med. Chem., 2003, 46, 2345.CrossRefPubMedGoogle Scholar
  13. 13.
    R. Li, K. Evaul, K. K. Sharma, K. H. Chang, J. Yoshimoto, J. Liu, R. J. Auchus, N. Sharifi, Clin. Cancer Res., 2012, 18, 3571.CrossRefPubMedGoogle Scholar
  14. 14.
    H. S. Soifer, N. Souleimanian, S. Wu, A. M. Voskresenskiy, F. K. Collak, B. Cinar, C. A. Stein, J. Biol. Chem., 2012, 287, 3777.CrossRefPubMedGoogle Scholar
  15. 15.
    J. Richards, A. C. Lim, C. W. Hay, A. E. Taylor, A. Wingate, K. Nowakowska, C. Pezaro, S. Carreira, J. Goodall, W. Arlt, I. J. McEwan, J. S. de Bono, G. Attard, Cancer Res., 2012, 72, 2176.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    H. Grossebrummel, T. Peter, R. Mandelkow, M. Weiss, D. Muzzio, U. Zimmermann, R. Walther, F. Jensen, C. Knabbe, M. Zygmunt, M. Burchardt, M. B. Stope, Int. J. Oncol., 2016, 48,793.CrossRefPubMedGoogle Scholar
  17. 17.
    R. D. Bruno, T. D. Gover, A. M. Burger, A. M. Brodie, V. C. Njar, Mol. Cancer Ther., 2008, 7, 2828.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    R. D. Bruno, T. S. Vasaitis, L. K. Gediya, P. Purushottamachar, A. M. Godbole, Z. Ates-Alagoz, A. M. Brodie, V. C. Njar, Steroids, 2011, 76, 1268.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    E. Djurendic, J. Daljev, M. Sakac, J. Canadi, S. J. Šanta, S. Andric, O. Klisuric, V. Kojic, G. Bogdanovic, M. Djurendic-Brenesel, S. Novakovic, K. P. Gaši, Steroids, 2008, 73,129.CrossRefPubMedGoogle Scholar
  20. 20.
    E. A. Djurendic, J. J. Ajdukovic, M. N. Sakac, J. J. Csanádi, V. V. Kojic, G. M. Bogdanovic, K. M. Penov Gaši, Eur. J. Med. Chem., 2012, 54,784.CrossRefPubMedGoogle Scholar
  21. 21.
    J. J. Ajdukovic, E. A. Djurendic, E. T. Petri, O. R. Klisuric, A. S. Celic, M. N. Sakac, D. S. Jakimov, K. M. Gaši, Bioorg. Med. Chem., 2013, 21, 7257.CrossRefPubMedGoogle Scholar
  22. 22.
    S. V. Stulov, Y. V. Tkachev, R. A. Novikov, M. G. Zavialova, V. P. Timofeev, A. Y. Misharin, Steroids, 2012, 77,77.CrossRefPubMedGoogle Scholar
  23. 23.
    S. V. Stulov, O. V. Mankevich, R. A. Novikov, Y. V. Tkachev, V. P. Timofeev, N. O. Dugin, V. F. Pozdnev, I. V. Fedyushkina, D. S. Scherbinin, A. V. Veselovsky, A. Y. Misharin, Steroids, 2013, 78,521.CrossRefPubMedGoogle Scholar
  24. 24.
    V. A. Kostin, V. A. Zolottsev, A. V. Kuzikov, R. A. Masa mrekh, V. V. Shumyantseva, A. V. Veselovsky, S. V. Stulov, R. A. Novikov, V. P. Timofeev, A. Y. Misharin, Steroids, 2016, 115,114.CrossRefPubMedGoogle Scholar
  25. 25.
    A. V. Kuzikov, N. O. Dugin, S. V. Stulov, D. S. Shcherbinin, M. S. Zharkova, Y. V. Tkachev, V. P. Timofeev, A. V. Veselovsky, V. V. Shumyantseva, A. Y. Misharin, Steroids, 2014, 88,66.CrossRefPubMedGoogle Scholar
  26. 26.
    N. Szabó, J. Ajdukovic, E. Djurendic, M. Sakac, I. Ignáth, J. Gardi, G. Mahmoud, O. Klisuric, S. Jovanovic-Šanta, K. Penov Gaši, M. Szécsi, Acta Biol. Hung., 2015, 66,41.CrossRefPubMedGoogle Scholar
  27. 27.
    V. A. Zolottsev, V. A. Kostin, R. A. Novikov, Ya. V. Tkachev, M. G. Zav´yalova, M. O. Taratynova, A. S. Latysheva, O. V. Zazulina, V. P. Timofeev, A. Yu. Misharin, Russ. Chem. Bull., 2018, 67,667.CrossRefGoogle Scholar
  28. 28.
    T. A. Pechurskaya, O. P. Lukashevich, A. A. Gilep, S. A. Usanov, Biochemistry (Moscow), 2008, 73,806.CrossRefGoogle Scholar
  29. 29.
    V. Zoete, M. A. Cuendet, A. Grosdidier, O. Michielin, J. Comput. Chem., 2011, 32, 2359.CrossRefPubMedGoogle Scholar
  30. 30.
    K. Shahrokh, A. Orendt, G. Yost, T. Cheatham, J. Comput. Chem., 2012, 33,119.CrossRefPubMedGoogle Scholar
  31. 31.
    W. Humphrey, A. Dalke, K. Schulten, J. Mol. Graph., 1996, 14,33.CrossRefPubMedGoogle Scholar
  32. 32.
    J. C. Phillips, R. Braun, W. Wang, J. Gumbart, E. Tajkhorshid, E. Villa, C. Chipot, R. D. Skeel, L. Kalé, K. Schulten, J. Comput. Chem., 2005, 26, 1781.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    T. Mosmann, J. Immunol. Methods, 1983, 65,55.CrossRefPubMedGoogle Scholar
  34. 34.
    V. V. Shumyantseva, T. V. Bulko, Y. O. Rudakov, G. P. Kuznetsova, N. F. Samenkova, A. V. Lisitsa, I. I. Karuzina, A. I. Archakov, J. Inorg. Biochem., 2007, 101,859.CrossRefPubMedGoogle Scholar
  35. 35.
    V. V. Shumyantseva, T. V. Bulko, E. V. Suprun, Y. M. Chalenko, M. Y. Vagin, Y. O. Rudakov, M. A. Shatskaya, A. I. Archakov, Biochim. Biophys. Acta, 2011, 1814,94.CrossRefPubMedGoogle Scholar
  36. 36.
    V. V. Shumyantseva, T. V. Bulko, A. Y. Misharin, A. I. Archakov, Biochemistry (Moscow), Suppl. Series B. Med. Chem., 2011, 5,55.CrossRefGoogle Scholar
  37. 37.
    K. P. Conner, C. Woods, W. M. Atkins, Arch. Biochem. Biophys., 2011, 507, 56.CrossRefPubMedGoogle Scholar

Copyright information

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

Authors and Affiliations

  • V. A. Kostin
    • 1
  • A. S. Latysheva
    • 1
  • V. A. Zolottsev
    • 1
  • Ya. V. Tkachev
    • 2
  • V. P. Timofeev
    • 2
  • A. V. Kuzikov
    • 1
  • V. V. Shumyantseva
    • 1
  • G. E. Morozevich
    • 1
  • A. Yu. Misharin
    • 1
  1. 1.V. N. Orekhovich Research Institute of Biomedical ChemistryRussian Academy of Medical SciencesMoscow, Russian FederationRussia
  2. 2.V. A. Engel’gardt Institute of Molecular BiologyRussian Academy of SciencesMoscow, Russian FederationRussia

Personalised recommendations