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

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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.

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References

  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.

  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.

  3. F. K. Yoshimoto, R. J. Auchus, J. Steroid Biochem. Mol. Biol., 2015, 151,52.

    Article  CAS  PubMed  Google Scholar 

  4. A. B. Alex, S. K. Pal, N. Agarwal, Ther. Adv. Med. Oncol., 2016, 8,267.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. L. Gomez, J. R. Kovac, D. J. Lamb, Steroids, 2015, 95,80.

    Article  CAS  PubMed  Google Scholar 

  6. R. D. Bruno, V. C. Njar, Bioorg. Med. Chem., 2007, 15, 5047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. E. Baston, F. R. Leroux, Rec. Pat. Anticancer Drug Discov., 2007, 2,31.

    Article  CAS  Google Scholar 

  8. C. P. Owen, Anticancer Agents Med. Chem., 2009, 9,613.

    Article  CAS  PubMed  Google Scholar 

  9. V. M. Moreira, J. A. Salvador, T. S. Vasaitis, V. C. Njar, Curr. Med. Chem., 2008, 15,868.

    Article  CAS  PubMed  Google Scholar 

  10. J. A. Salvador, R. M. Pinto, S. M. Silvestre, J. Steroid Biochem. Mol. Biol., 2013, 137,199.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  17. R. D. Bruno, T. D. Gover, A. M. Burger, A. M. Brodie, V. C. Njar, Mol. Cancer Ther., 2008, 7, 2828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  22. S. V. Stulov, Y. V. Tkachev, R. A. Novikov, M. G. Zavialova, V. P. Timofeev, A. Y. Misharin, Steroids, 2012, 77,77.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  28. T. A. Pechurskaya, O. P. Lukashevich, A. A. Gilep, S. A. Usanov, Biochemistry (Moscow), 2008, 73,806.

    Article  CAS  Google Scholar 

  29. V. Zoete, M. A. Cuendet, A. Grosdidier, O. Michielin, J. Comput. Chem., 2011, 32, 2359.

    Article  CAS  PubMed  Google Scholar 

  30. K. Shahrokh, A. Orendt, G. Yost, T. Cheatham, J. Comput. Chem., 2012, 33,119.

    Article  CAS  PubMed  Google Scholar 

  31. W. Humphrey, A. Dalke, K. Schulten, J. Mol. Graph., 1996, 14,33.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. T. Mosmann, J. Immunol. Methods, 1983, 65,55.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  36. V. V. Shumyantseva, T. V. Bulko, A. Y. Misharin, A. I. Archakov, Biochemistry (Moscow), Suppl. Series B. Med. Chem., 2011, 5,55.

    Article  Google Scholar 

  37. K. P. Conner, C. Woods, W. M. Atkins, Arch. Biochem. Biophys., 2011, 507, 56.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. V. N. Orekhovich Research Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Build. 8, 10 Pogodinskaya ul., 119121, Moscow, Russian Federation, Russia

    V. A. Kostin, A. S. Latysheva, V. A. Zolottsev, A. V. Kuzikov, V. V. Shumyantseva, G. E. Morozevich & A. Yu. Misharin

  2. V. A. Engel’gardt Institute of Molecular Biology, Russian Academy of Sciences, 32 ul. Vavilova, 119991, Moscow, Russian Federation, Russia

    Ya. V. Tkachev & V. P. Timofeev

Authors
  1. V. A. Kostin
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  2. A. S. Latysheva
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  3. V. A. Zolottsev
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  4. Ya. V. Tkachev
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  5. V. P. Timofeev
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  6. A. V. Kuzikov
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  7. V. V. Shumyantseva
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  8. G. E. Morozevich
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  9. A. Yu. Misharin
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Corresponding author

Correspondence to V. A. Zolottsev.

Additional information

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 0682–0687, April, 2018.

Based on the materials of the III Interdisciplinary Symposium on Medicinal, Organic, and Biological Chemistry and Pharmaceuticals (MOBI-ChemPharm-2017; May 28–31, 2017; Sevastopol, Russia).

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Kostin, V.A., Latysheva, A.S., Zolottsev, V.A. et al. Oxazoline derivatives of [17(20)E]-21-norpregnene – inhibitors of CYP17A1 activity and proliferation of prostate carcinoma cells. Russ Chem Bull 67, 682–687 (2018). https://doi.org/10.1007/s11172-018-2122-7

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  • DOI: https://doi.org/10.1007/s11172-018-2122-7

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