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New Δ8(14)-15-Ketosterols with an Oxygenated Side Chain

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Abstract

New analogues of 3β-hydroxy-5α-cholest-8(14)-en-15-one (15-ketosterol) with modified 17-chains [(22S,23S,24S)- and (22R,23R,24S)-3β-hydroxy-24-methyl-22,23-oxido-5α -cholest-8(14)-en-15- ones and (22RS,23ξ,24S)-24-methyl-5α-cholesta-8(14)-ene-3β, 22,23-triol-15-one] were synthesized from (22E,24S)-3β-acetoxy-24-methyl-5α-cholesta-8(14), 22-dien-15-one. The chiralities of their 22 and 23 centers were determined by NMR spectroscopy. The isomeric 22,23-epoxides effectively inhibited cholesterol biosynthesis in hepatoma Hep G2 cells (IC50 0.9±0.2 and 0.7±0.2 μM, respectively), and their activities significantly exceeded those of 15-ketosterol (IC50 4.0±0.5 μM), (22E,24S)-3β-hydroxy-24-methyl-5α-cholesta-8(14),22- dien-15-one (IC50 3.1±0.4 μM), and the 3β,22,23-triol synthesized (IC50 6.0±1.0 μM).

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Abbreviations

CPBA:

m-chloroperbenzoic acid

FSC:

calf fetal serum

PBS:

phosphate buffered saline

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Authors and Affiliations

  1. Orekhovich Institute of Biomedical Chemistry, Russian Academy of Medical Sciences, Pogodinskaya ul. 10, Moscow, 119992, Russia

    H. Yu. Flegentov, E. A. Piir, N. V. Medvedeva & A. Yu. Misharin

  2. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, Moscow, 117990, Russia

    Ya. V. Tkachev & V. P. Timofeev

Authors
  1. H. Yu. Flegentov
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  2. E. A. Piir
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  3. N. V. Medvedeva
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  4. Ya. V. Tkachev
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  5. V. P. Timofeev
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  6. A. Yu. Misharin
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Corresponding author

Correspondence to A. Yu. Misharin.

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__________

Translated from Bioorganicheskaya Khimiya, Vol. 31, No. 3, 2005, pp. 312–319.

Original Russian Text Copyright © 2005 by Flegentov, Piir, Medvedeva, Tkachev, Timofeev, Misharin.

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Flegentov, H.Y., Piir, E.A., Medvedeva, N.V. et al. New Δ8(14)-15-Ketosterols with an Oxygenated Side Chain. Russ J Bioorg Chem 31, 279–285 (2005). https://doi.org/10.1007/s11171-005-0038-0

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  • DOI: https://doi.org/10.1007/s11171-005-0038-0

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