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

  • L. A. KaluzhskiyEmail author
  • 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
Article

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.

Keywords

surface plasmon resonance optical biosensor spectral titration cytochrome P450 CYP51 triterpenes 

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Copyright information

© Pleiades Publishing, Ltd. 2014

Authors and Affiliations

  • L. A. Kaluzhskiy
    • 1
    Email author
  • O. V. Gnedenko
    • 1
  • A. A. Gilep
    • 2
  • N. V. Strushkevich
    • 2
  • T. V. Shkel
    • 2
  • M. A. Chernovetsky
    • 3
  • A. S. Ivanov
    • 1
  • A. V. Lisitsa
    • 1
  • A. S. Usanov
    • 2
  • V. A. Stonik
    • 4
  • A. I. Archakov
    • 1
  1. 1.Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Medical SciencesMoscowRussia
  2. 2.Institute of Bioorganic Chemistry of the National Academy of Sciences of BelarusMinskBelarus
  3. 3.National Research Center for Pediatric Oncology, Hematology and ImmunologyMinsk region, BorovlyanyBelarus
  4. 4.Elyakov Pacific Institute of Bioorganic ChemistryFar Eastern Branch of the Russian Academy of SciencesVladivostokRussia

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