2,3-Dihydrowithaferin A-3β-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somnifera

Ya ming Xu, Marilyn T. Marron, Emily Seddon, Steven P. McLaughlin, Dennis T. Ray, Luke Whitesell, A. A. Leslie Gunatilaka

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Preparations of the roots of the medicinal plant Withania somnifera (L.) Dunal commonly called ashwagandha have been used for millennia in the Ayurvedic medical tradition of India as a general tonic to relieve stress and enhance health, especially in the elderly. In modern times, ashwagandha has been shown to possess intriguing antiangiogenic and anticancer activity, largely attributable to the presence of the steroidal lactone withaferin A as the major constituent. When cultured using the aeroponic technique, however, this plant was found to produce a new natural product, 2,3-dihydrowithaferin A-3β-O-sulfate (1), as the predominant constituent of methanolic extracts prepared from aerial tissues. The characteristic bioactivities exhibited by 1 including inhibition of cancer cell proliferation/survival, disruption of cytoskeletal organization and induction of the cellular heat-shock response paralleled those displayed by withaferin A (2). The delayed onset of action and reduced potency of 1 in cell culture along with previous observations demonstrating the requirement of the 2(3)-double bond in withanolides for bioactivity suggested that 1 might be converted to 2 in cell culture media and this was confirmed by HPLC analysis. The abundant yield of 1 from aeroponically cultivated plants, its good aqueous solubility and spontaneous conversion to 2 under cell culture conditions, suggest that 1 could prove useful as a readily formulated prodrug of withaferin A that merits further evaluation in animal models.

Original languageEnglish (US)
Pages (from-to)2210-2214
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number6
DOIs
StatePublished - Mar 15 2009

Keywords

  • 2,3-Dihydrowithaferin A-3β-O-sulfate
  • Aeroponic culture
  • Anticancer activity
  • Cytoskeletal reorganization
  • Heat-shock induction
  • Prodrug

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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