title: 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.
authors.forename: József
authors.initials: J
authors.lastname: Csábi
authors.affiliation: Department of Genome Medicine, Kaohsiung Medical University , Kaohsiung 807, Taiwan, Republic of China.
authors.forename: Tusty-Jiuan
authors.initials: TJ
authors.lastname: Hsieh
authors.forename: Feria
authors.initials: F
authors.lastname: Hasanpour
authors.forename: Ana
authors.initials: A
authors.lastname: Martins
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kele
authors.affiliation: Department of Inorganic and Analytical Chemistry, NMR Group, Budapest University of Technology and Economics , 1111 Budapest, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Gáti
authors.affiliation: Department of Inorganic and Analytical Chemistry, NMR Group, Budapest University of Technology and Economics , 1111 Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Simon
authors.affiliation: Department of Inorganic and Analytical Chemistry, NMR Group, Budapest University of Technology and Economics , 1111 Budapest, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Tóth
authors.forename: Attila
authors.initials: A
authors.lastname: Hunyadi
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D034821:Commelinaceae / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D004441:Ecdysterone / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation; D018517:Plant Roots / Q000737:chemistry; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004365:Drugs, Chinese Herbal; D004441:Ecdysterone; D051057:Proto-Oncogene Proteins c-akt