title: Biochemical mode of action and differential activity of new ecdysone agonists against mosquitoes and moths.
abstract: THQ (1-aroyl-4-(arylamino)-1,2,3,4-tetrahydroquinoline) compounds were identified by FMC Corporation in cell-based assays that used ecdysone receptors from Drosophila melanogaster, Heliothis virescens, or Plodia interpunctata. THQ compounds showed weak insecticidal activity against H. virescens and, therefore, were not developed further. Several ecdysone agonists based on THQ chemotype have been synthesized and tested for their activity against a number of EcRs in transactivation assays. The THQ compound, RG-120768, activated AaEcR (EcR from A. aegypti) but did not activate EcRs cloned from other insects. In transactivation assays, all six THQ ligands tested functioned through AaEcR but not through CfEcR (EcR from Choristoneura fumiferana). Three THQ compounds that showed higher activity in transactivation assays were tested in tobacco bud moth, H. virescens, and yellow fever mosquito, A. aegypti. These compounds showed higher activity in A. aegypti when compared to their activity in H. virescens. These data show that the THQ ligands are a new class of non-steroidal ecdysone agonists with preferential activity against mosquitoes.
authors.affiliation: Department of Entomology, S225 Agricultural Science Center, College of Agriculture, University of Kentucky, Lexington, KY 40546, USA. rpalli@uky.edu
authors.forename: S R
authors.initials: SR
authors.lastname: Palli
authors.forename: C M
authors.initials: CM
authors.lastname: Tice
authors.forename: V M
authors.initials: VM
authors.lastname: Margam
authors.forename: A M
authors.initials: AM
authors.lastname: Clark
mesh_terms: D016475:3T3 Cells; D000330:Aedes; D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D003001:Cloning, Molecular; D007306:Insecticides / Q000494:pharmacology*; D051379:Mice; D009036:Moths; D011987:Receptors, Steroid / Q000819:agonists* / Q000235:genetics; D013045:Species Specificity; D015533:Transcriptional Activation
chemical_list: D000634:Aminoquinolines; D007306:Insecticides; C501284:RG 120768; D011987:Receptors, Steroid; C055469:ecdysone receptor