Oxidized Metabolites of 20-Hydroxyecdysone and Their Activity on Skeletal Muscle Cells: Preparation of a Pair of Desmotropes with Opposite Bioactivities
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.
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CAL activates Akt signaling more strongly than 20E in murine skeletal muscle cells.
“CAL was synthesized in-house via base-catalyzed autoxidation of 20E and has previously been shown to activate Akt signaling more strongly in murine skeletal muscle cells than 20E [21], suggesting enhanced anabolic potential.”
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“CAL was synthesized in-house via base-catalyzed autoxidation of 20E and has previously been shown to activate Akt signaling more strongly in murine skeletal muscle cells than 20E [21], suggesting enhanced anabolic potential.”
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- Authors
- Csábi, J., Hsieh, T.-J., Hasanpour, F., Martins, A., Kele, Z., Gáti, T., Simon, A., Tóth, G., & Hunyadi, A.
- Affiliations
- University of Szeged (HU)
- Kaohsiung Medical University (TW)
- Budapest University of Technology and Economics (HU)
- Corresponding author
- Hunyadi, Attila
- ORCID
- Venue
- Journal of Natural Products
- Publisher
- American Chemical Society (ACS)
- Published
- 2015-10-14
- Volume
- 78
- Issue
- 10
- Pages
- 2339-2345
- ISSN
- 0163-3864 (ISSN-L)
- 1520-6025
- OpenAlex
- W2239530257
- Semantic Scholar
- 88587e6e855693c97020c36df662f24aa4857d4f
- Cited by
- 27
- References
- 22
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 2 · 2015: 1
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Natural Products (publishedVersion)
- PubMed (publishedVersion)
- SZTE Publicatio Repozitórium (University of Szeged) (submittedVersion)
- Funders
- European Cooperation in Science and Technology (CM1407)
- National Science Council Taiwan (NSC 101-2314-B-037-033)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Steroid Chemistry and Biochemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical Studies and Bioactivities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Natural product bioactivities and synthesis
- Keywords
- 20-hydroxyecdysone, phytoecdysteroids, autoxidation, Akt phosphorylation, skeletal muscle cells, metabolite synthesis
- MeSH terms
- Animals, Chromatography, High Pressure Liquid, Drugs, Chinese Herbal, Ecdysterone, Oxidation-Reduction, Phosphorylation, Molecular Structure, Signal Transduction, Muscle, Skeletal, Muscle Fibers, Skeletal, Plant Roots, Commelinaceae, Proto-Oncogene Proteins c-akt, Mice
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