title: 8-O-acetylharpagide is a nonsteroidal ecdysteroid agonist.
abstract: We have identified a novel nonsteroidal ecdysteroid agonist. This compound was isolated from a methanol extract of Ajuga reptans L. (Lamiaceae) and the structure was identified by spectroscopic methods as 8-O-acetylharpagide. We have characterised this compound as an ecdysteroid agonist in a transactivation assay using beta-galactosidase as the reporter gene regulated by ecdysteroid response elements. In this assay, 8-O-acetylharpagide has an EC50 of 22 microM. The compound also competes with tritiated-ponasterone A for binding to the Drosophila ecdysteroid receptor. Finally, it induces differentiation of Drosophila Kc cells as would be expected of an ecdysteroid agonist. This iridoid glycoside is common to several plant species and may play a role in the natural defense mechanisms of plants.
authors.affiliation: Department of Genetics and Molecular Biology, Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: A
authors.initials: A
authors.lastname: Elbrecht
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Jurgens
authors.forename: O D
authors.initials: OD
authors.lastname: Hensens
authors.forename: D L
authors.initials: DL
authors.lastname: Zink
authors.forename: H T
authors.initials: HT
authors.lastname: Beck
authors.forename: M J
authors.initials: MJ
authors.lastname: Balick
authors.forename: R
authors.initials: R
authors.lastname: Borris
mesh_terms: D000818:Animals; D004330:Drosophila / Q000378:metabolism; D004441:Ecdysterone / Q000819:agonists* / Q000378:metabolism; D007301:Insect Hormones; D015394:Molecular Structure; D010936:Plant Extracts; D010944:Plants / Q000378:metabolism*; D011714:Pyrans / Q000737:chemistry / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism
chemical_list: D007301:Insect Hormones; D010936:Plant Extracts; D011714:Pyrans; D011987:Receptors, Steroid; C034808:ecdysteroid receptor; D004441:Ecdysterone; C077626:8-O-acetylharpagide