Akt-dependent anabolic activity of natural and synthetic brassinosteroids in rat skeletal muscle cells

Debora Esposito, Thirumurugan Rathinasabapathy, Alexander Poulev, Slavko Komarnytsky, Ilya Raskin

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Brassinosteroids are plant-derived polyhydroxylated derivatives of 5α-cholestane, structurally similar to cholesterol-derived animal steroid hormones and insect ecdysteroids. In this study, we synthesized a set of brassinosteroid analogues of a natural brassinosteroid (22S,23S)- homobrassinolide (HB, 1), including (22S,23S)-homocastasterone (2), (22S,23S)-3α-fluoro-homobrasinolide (3), (22S,23S)-3α-fluoro- homocastasterone (4), (22S,23S)-7-aza-homobrassinolide (5), and (22S,23S)-6-aza-homobrassinolide (6) and studied their anabolic efficacy in the L6 rat skeletal muscle cells in comparison to other synthetic and naturally occurring brassinosteroids (22R,23R)-homobrassinolide (7), (22S,23S)- epibrassinolide (8), and (22R,23R)-epibrassinolide (9). Presence of the 6-keto group in the B ring and stereochemistry of 22α,23α-vicinal hydroxyl groups in the side chain were critical for the anabolic activity, possibly due to higher cytotoxicity of the 22β,23β-hydroxylated brassinosteroids. All anabolic brassinosteroids tested in this study selectively activated PI3K/Akt signaling pathway as evident by increased Akt phosphorylation in vitro. Plant brassinosteroids and their synthetic derivatives may offer a novel therapeutic strategy for promoting growth, repair, and maintenance of skeletal muscles.

Original languageEnglish (US)
Pages (from-to)4057-4066
Number of pages10
JournalJournal of Medicinal Chemistry
Volume54
Issue number12
DOIs
StatePublished - Jun 23 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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