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Synthesis and Evaluation of N-Alkynylaminosteroids as Potential Inhibitors of CYP450 17A1

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Abstract—

Four isomeric N-alkynylaminosteroids of the androstane and pregnane series were synthesized and tested in vitro for inhibition of CYP450 17A1 heterologously expressed in transgenic yeast Yarrowia lipolytica. The highest inhibitory activity was observed in the case of steroids containing a side chain of five atoms. At equal concentrations of the substrate and the inhibitor (50 μM), the pregnenolone derivative containing the N-propynyl fragment caused a 5-fold decrease of reduced the progesterone conversion.

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ACKNOWLEDGMENTS

The authors are grateful to the staff of the Belarusian-Dutch joint venture Farmland OJSC for providing a sample of abiraterone acetate, the colleagues working at the Department of Radiation Chemistry and Chemical Pharmaceutical Technologies and the Department of Organic Chemistry (Faculty of Chemistry, Belarusian State University) for the opportunity to perform spectroscopic analysis.

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Correspondence to V. M. Shkumatov.

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This article does not contain any research involving humans or using animals as objects.

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Translated by A. Medvedev

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Panada, J.U., Faletrov, Y.V., Frolova, N.S. et al. Synthesis and Evaluation of N-Alkynylaminosteroids as Potential Inhibitors of CYP450 17A1. Biochem. Moscow Suppl. Ser. B 13, 357–363 (2019). https://doi.org/10.1134/S1990750819040073

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Keywords:

  • alkyne steroid
  • steroid 17-alpha-hydroxylase/17,20-lyase inhibition
  • transgenic yeast
  • molecular docking
  • androgen-dependent tumors