Screening of novel indole steroids as cytochrome P450 substrates in silico

Authors

  • Ян U. Panada Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus
  • Yaroslav V. Faletrov Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus
  • Nina S. Frolova Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus
  • Vladimir M. Shkumatov Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus

Keywords:

indole steroids, cytochrome P450, molecular docking

Abstract

In this work we describe the modeling of interactions between indole steroids and steroidogenic cytochromes P450. The highest possible affinity is expected of enzymes involved in cholesterol transformation (i. e. CYP3A4, CYP7A1, CYP11A1). In case of pregnane and estrane-converting proteins a decrease in the binding energy of synthetic steroids is found. The variations in affinity are explained in terms of structural difference. These calculations imply that indole steroids are most likely to be hydroxylated at positions 4 and 7 as well as interfere with CYP17A1 activity by heme coordination.

Author Biographies

  • Ян U. Panada, Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus

    junior researcher at the laboratory of biochemistry of drugs

  • Yaroslav V. Faletrov, Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus

    PhD (chemistry); leading researcher at the laboratory of biochemistry of drugs

  • Nina S. Frolova, Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus

    researcher at the laboratory of biochemistry of drugs

  • Vladimir M. Shkumatov, Institute for Physical Chemical Problems, Belarusian State University, 14 Lieninhradskaja Street, Minsk 220006, Belarus

    corresponding member of the Natio nal Academy of Sciences of Belarus, doctor of science (biology), full professor; head of the laboratory of biochemistry of drugs

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Published

2018-04-30

Issue

No. 1 (2018): Journal of the Belarusian State University. Chemistry

Section

Original Articles

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How to Cite

[1]
Panada Я.U. et al. 2018. Screening of novel indole steroids as cytochrome P450 substrates in silico. Journal of the Belarusian State University. Chemistry. 1 (Apr. 2018), 28–34.