title: The ovicidal, larvacidal and adulticidal properties of 5,5'-dimethyl-2,2'-bipyridyl against Drosophila melanogaster.
abstract: Insecticide resistance has limited the number of available chemical options for insect pest control. Hence there is a need for new chemistries with novel modes of action. Here we investigate the mode of action for an insecticide that has not yet been released for commercial use. The ovicidal, larvacidal and adulticidal effects of 5,5'-dimethyl -2, 2'-dipyridyl (termed Ha44), which is being developed as a treatment for head lice, were evaluated in the Drosophila melanogaster model system. Ha44 demonstrated significant activity against embryos and was capable of arresting development at a number of stages of embryogenesis. The effects of Ha44 on embryos was shown to be reversible following the addition of the metal ions Fe(II) and Fe(III), Cu and Zn. When larvae were exposed to Ha44, lethality was recorded at similar concentrations to those observed for embryos. Using an eYFP reporter system it was shown that Ha44 was able to reduce the levels of both copper and zinc in the digestive tract, confirming the binding of Ha44 to these metals in vivo. Ha44 has further been shown to inhibit a zinc containing metalloproteinase in vitro. Exposure of adult flies to Ha44 resulted in lethality, but at higher concentrations than those observed for embryos and larvae. The median lethal dose in adult flies was shown to be associated with the type of exposure, with an LD-50 of 1.57 mM being recorded following the direct contact of flies with Ha44, while an LD-50 of 12.29 mM was recorded following the ingestion of the compound. The capacity of Ha44 to act on all stages of the life-cycle and potentially via a range of targets suggests that target site resistance is unlikely to evolve.
authors.affiliation: Department of Genetics, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia.
authors.forename: Matthias B
authors.initials: MB
authors.lastname: Van Hiel
authors.forename: Bert
authors.initials: B
authors.lastname: Breugelmans
authors.forename: Charles N
authors.initials: CN
authors.lastname: Pagel
authors.forename: Adam K
authors.initials: AK
authors.lastname: Williams
authors.forename: Aiden K
authors.initials: AK
authors.lastname: Varan
authors.forename: Richard
authors.initials: R
authors.lastname: Burke
authors.forename: Vernon M
authors.initials: VM
authors.lastname: Bowles
authors.forename: Philip
authors.initials: P
authors.lastname: Batterham
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003300:Copper / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000254:growth & development; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology; D007305:Insecticide Resistance / Q000187:drug effects / Q000235:genetics; D007306:Insecticides / Q000494:pharmacology*; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D007928:Lethal Dose 50; D008018:Life Cycle Stages; D015032:Zinc / Q000494:pharmacology
chemical_list: C524593:5,5'-dimethyl-2,2'-bipyridyl; D005290:Ferric Compounds; D007306:Insecticides; D015082:2,2'-Dipyridyl; D003300:Copper; D015032:Zinc