Oxidized Metabolites of 20-Hydroxyecdysone and Their Activity on Skeletal Muscle Cells: Preparation of a Pair of Desmotropes with Opposite Bioactivities

József Csábi, Tusty Jiuan Hsieh, Feria Hasanpour, Ana Martins, Z. Kele, Tamás Gáti, A. Simon, Gábor Tóth, Attila Hunyadi

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Increasing the activation of protein kinase B (Akt) has been suggested as a key signaling step in the nonhormonal anabolic activity of the phytoecdysteroid 20-hydroxyecdysone (20E) in mammals. Base-catalyzed autoxidation of this compound was shown previously to yield interesting B-ring-modified analogues. Herein is reported a thorough study on this reaction, resulting in the preparation and complete NMR spectroscopic assignments of calonysterone (5) and its previously overlooked desmotropic pair (7), along with two new sensitive metabolites of 20E. The two isomers showed considerable stability in solution. Time dependency of the reaction for yield optimization is also presented; by means of analytical HPLC, the two desmotropes can reach a maximum combined yield of >90%. The activity of these compounds on Akt phosphorylation was tested in murine skeletal muscle cells. Compounds 2 and 5 showed more potent activity than 20E in increasing Akt activation, while compound 7 exerted an opposite effect. As such, the present study provides the first direct evidence for a pair of desmotropes exerting significantly different bioactivities.

Original languageEnglish
Pages (from-to)2339-2345
Number of pages7
JournalJournal of Natural Products
Volume78
Issue number10
DOIs
Publication statusPublished - Oct 23 2015

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Ecdysterone
Proto-Oncogene Proteins c-akt
Metabolites
Bioactivity
Muscle Cells
Muscle
Mammals
Skeletal Muscle
Chemical activation
High Pressure Liquid Chromatography
Cells
Phosphorylation
Isomers
Nuclear magnetic resonance

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Pharmaceutical Science
  • Analytical Chemistry
  • Organic Chemistry
  • Molecular Medicine
  • Complementary and alternative medicine

Cite this

Oxidized Metabolites of 20-Hydroxyecdysone and Their Activity on Skeletal Muscle Cells : Preparation of a Pair of Desmotropes with Opposite Bioactivities. / Csábi, József; Hsieh, Tusty Jiuan; Hasanpour, Feria; Martins, Ana; Kele, Z.; Gáti, Tamás; Simon, A.; Tóth, Gábor; Hunyadi, Attila.

In: Journal of Natural Products, Vol. 78, No. 10, 23.10.2015, p. 2339-2345.

Research output: Contribution to journalArticle

Csábi, József ; Hsieh, Tusty Jiuan ; Hasanpour, Feria ; Martins, Ana ; Kele, Z. ; Gáti, Tamás ; Simon, A. ; Tóth, Gábor ; Hunyadi, Attila. / Oxidized Metabolites of 20-Hydroxyecdysone and Their Activity on Skeletal Muscle Cells : Preparation of a Pair of Desmotropes with Opposite Bioactivities. In: Journal of Natural Products. 2015 ; Vol. 78, No. 10. pp. 2339-2345.
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