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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
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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.

Key words

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

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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

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