title: Pro-insecticidal approach towards increasing in planta activity.
abstract: BACKGROUND
  The adrenergic mode of action was investigated for the development of potential new insecticides. Clonidine-related analogs were tested against Myzus persicae (Sulzer) and Bemisia tabaci (Gennadius). Clonidine analogs lack translation owing to a possible vacuole-trapping mechanism. Physical property modulation via a prodrug approach was attempted to overcome this mechanism.
  
  
  RESULTS
  Clonidine showed insecticidal activity against M. persicae and B. tabaci. A prodrug of a known open-chain analog of clonidine was developed. While the prodrug had decreased pKaand increased lipophilicity and displayed good activity against M. persicae B. tabaci, the activity did not translate to cotton. Metabolic studies showed that the prodrug was quickly metabolized to the parent compound, and was further metabolized to a known vacuole-trapped oxazoline analog.
  
  
  CONCLUSIONS
  Adrenergic active compounds, such as clonidine analogs, show potential as insecticides; however, a designed prodrug approach did not overcome the lack of translation in this case. Studies confirmed that the synthesized prodrug analog metabolized in planta to the proposed vacuole-trapped compound. One possible explanation for the failure of this approach is that the rate of metabolism and vacuole trapping is faster than translaminar flow, and therefore the released pesticide is not biologically available to the target organism. © 2016 Society of Chemical Industry.
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Lawrence C
authors.initials: LC
authors.lastname: Creemer
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Giampietro
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: William
authors.initials: W
authors.lastname: Lambert
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Maurice C
authors.initials: MC
authors.lastname: Yap
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Gerrit J
authors.initials: GJ
authors.lastname: deBoer
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Yelena
authors.initials: Y
authors.lastname: Adelfinskaya
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Castetter
authors.affiliation: Dow AgroSciences, Discovery Research, Indianapolis, IN, USA.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Wessels
mesh_terms: D000818:Animals; D001042:Aphids / Q000187:drug effects / Q000254:growth & development; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006430:Hemiptera / Q000187:drug effects* / Q000254:growth & development; D007306:Insecticides / Q000494:pharmacology*; D009758:Nymph / Q000187:drug effects; D018515:Plant Leaves / Q000502:physiology; D011679:Pupa / Q000187:drug effects
chemical_list: D007306:Insecticides; D003000:Clonidine
keywords: adrenergic; green peach aphid; metabolism; prodrug; translaminar; vacuole trapping; whitefly