title: Mosquitocidal carbamates with low toxicity to agricultural pests: an advantageous property for insecticide resistance management.
abstract: BACKGROUND
  Insecticide resistance in the malaria mosquito Anopheles gambiae is well documented, and widespread agricultural use of pyrethroids may exacerbate development of resistance when pyrethroids are used in vector control. We have developed carbamate anticholinesterases that possess a high degree of An. gambiae:human selectivity for enzyme inhibition. The purpose of this study was to assess the spectrum of activity of these carbamates against other mosquitoes and agricultural pests.
  
  
  RESULTS
  Experimental carbamates were potent inhibitors of mosquito acetylcholinesterases, with IC50 values in the nanomolar range. Similar potencies were observed for Musca domestica and Drosophila melanogaster enzymes. Although meta-substituted carbamates were potent inhibitors, two ortho-substituted carbamates displayed poor enzyme inhibition (IC50 ≥ 10(-6)  M) in honey bee (Apis mellifera), Asian citrus psyllid (Diaphorina citri) and lepidopteran agricultural pests (Plutella xylostella and Ostrinia nubilalis). Enzyme inhibition results were confirmed by toxicity studies in caterpillars, where the new carbamates were 2-3-fold less toxic than propoxur and up to tenfold less active than bendiocarb, indicating little utility of these compounds for crop protection.
  
  
  CONCLUSIONS
  The experimental carbamates were broadly active against mosquito species but not agricultural pests, which should mitigate selection for mosquito insecticide resistance by reducing agricultural uses of these compounds. © 2014 Society of Chemical Industry.
authors.affiliation: University of Florida, Department of Entomology and Nematology, Emerging Pathogens Institute, Gainesville, FL, USA.|Vanderbilt University School of Medicine, Department of Anesthesiology and Pharmacology, Nashville, TN, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Swale
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Carlier
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Hartsel
authors.affiliation: Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Ma
authors.affiliation: University of Florida, Department of Entomology and Nematology, Emerging Pathogens Institute, Gainesville, FL, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bloomquist
mesh_terms: D000818:Animals; D000852:Anopheles / Q000187:drug effects; D002219:Carbamates / Q000494:pharmacology* / Q000633:toxicity; D007313:Insecta / Q000187:drug effects* / Q000254:growth & development; D007305:Insecticide Resistance; D007306:Insecticides / Q000494:pharmacology* / Q000633:toxicity; D007814:Larva / Q000187:drug effects
chemical_list: D002219:Carbamates; D007306:Insecticides
keywords: Anopheles gambiae; acetylcholinesterase; mosquito; selectivity