Assessment of novel inhibitors of Helicoverpa aminopeptidases as anti-insect agents.
Helicoverpa species present problems worldwide as pests on a variety of agricultural crops. In Australia, the costs of controlling H. armigera (Hübn.) and H. punctigera (Wall.) are a major burden on the cotton industry, and novel mechanisms are continually sought to combat these pests. Potential new targets for insecticides are the digestive proteases of the insect, including the aminopeptidases (APs). A variety of compounds, designed to be similar in structure to known AP inhibitors, were synthesized and screened for activity in inhibiting H. armigera larval growth and AP activity. The most effective compounds in both assays proved to be hydroxamic acids and methylphosphonic acids. Compounds that incorporated both of these groups were also found to have significant potential as control agents. The most inhibitory compounds included valine methylphosphonic acid and a leucine methylphosphonic acid/hydroxamic acid derivative. The valine methylphosphonic acid compound was tested further in vitro, with the aim of producing a new active capable of restricting the viability of Helicoverpa populations on commercial crops.
Duncan
Ann-Maree
AM
Department of Agricultural Sciences, La Trobe University, Bundoora, Victoria, Australia.
Ren
Hua
H
Bound
Fleur
F
Tully
Jon
J
Chandler
David S
DS
Sandeman
R Mark
RM
D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D006877:Hydroxamic Acids / Q000737:chemistry; D007306:Insecticides / Q000032:analysis*; D007814:Larva; D009036:Moths; D063065:Organophosphonates / Q000737:chemistry; D009943:Organophosphorus Compounds / Q000737:chemistry; D010797:Phthalimides / Q000737:chemistry; D044024:Tetralones / Q000737:chemistry; D014633:Valine / Q000031:analogs & derivatives / Q000737:chemistry
D006877:Hydroxamic Acids; D007306:Insecticides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D010797:Phthalimides; D044024:Tetralones; C515648:valine methyl phosphonate; C032627:methylphosphonic acid; D000626:Aminopeptidases; D014633:Valine; C010531:actinonin