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Synthesis of 19-hydroxypregn-4-en-20-one and 19-hydroxy-5β-pregn-3-en-20-one that selectively bind to membrane progesterone receptors, and assessment of their immunomodulatory effects

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Abstract

A new approach to the synthesis of isomeric 19-hydroxypregn-4-en-20-one (1) and 19-hydroxy-5β-pregn-3-en-20-one (2), the selective ligands of membrane progesterone receptors, in a ratio of 1.5:1 is presented. The effect of these steroids on the gene expression of several cytokines (TNFα, IL-1β, IL-6, and TGFβ) in K562 cells was studied. Progesterone and compound 1 acted unidirectionally, significantly decreasing the TGFβ mRNA levels in these cells. The highest activity was exhibited by compound 2 which regulated the expression of the three studied genes, increasing the level of TNFα mRNA and IL-1β mRNA and decreasing the level of TGFβ mRNA. The immunomodulatory effect of the synthesized selective ligands of membrane progesterone receptors found in K562 cells is comparable (for 1) or even surpasses (for 2) the effect of a natural hormone.

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Funding

The biological part of the work was financially supported by the Russian Foundation for Basic Research (Project No. 20-015-00092).

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Authors and Affiliations

  1. N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky prosp., 119991, Moscow, Russian Federation

    I. S. Levina, Yu. V. Kuznetsov & I. V. Zavarzin

  2. Department of Biology, M. V. Lomonosov Moscow State University, 1/12 Leninskie Gory, 119234, Moscow, Russian Federation

    T. A. Shchelkunova & A. V. Polikarpova

Authors
  1. I. S. Levina
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  2. T. A. Shchelkunova
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  3. A. V. Polikarpova
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  4. Yu. V. Kuznetsov
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  5. I. V. Zavarzin
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Corresponding author

Correspondence to I. S. Levina.

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Dedicated to Academician of the Russian Academy of Sciences O. M. Nefedov on the occasion of his 90th birthday.

Published in Russian in Izyestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2227–2232, November, 2021.

This article does not contain a description of studies using animals or people as objects.

The authors declare that there is no conflict of interests in the financial or any other sphere.

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Levina, I.S., Shchelkunova, T.A., Polikarpova, A.V. et al. Synthesis of 19-hydroxypregn-4-en-20-one and 19-hydroxy-5β-pregn-3-en-20-one that selectively bind to membrane progesterone receptors, and assessment of their immunomodulatory effects. Russ Chem Bull 70, 2227–2232 (2021). https://doi.org/10.1007/s11172-021-3337-6

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  • DOI: https://doi.org/10.1007/s11172-021-3337-6

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