Resistance-Breaking Insecticidal Activity of New Spatial Insecticides against .

The use of N-aryl amide derivatives as spatially acting insecticides remains relatively unexplored. To expand this knowledge, we synthesized eighty-nine N-aryl amide analogues and screened them for mortality against an insecticide-susceptible strain of mosquitoes, Orlando (OR), using a vapor exposure glass tube assay. Of the screened compounds, twenty-two produced >92% mortality at 24 h and warranted further investigation to determine LC values. Fifteen of these analogues had LC values within 2 orders of magnitude of transfluthrin, and of significant interest, -(2,6-dichloro-4-(trifluoromethyl)phenyl)-2,2,3,3,3-pentafluoropropanamide (compound ) was nearly as potent as transfluthrin and exhibited greater toxicity than metofluthrin when screened against OR . Compounds exhibiting potent toxicity against OR or whose structure-activity relationship potentially offered beneficial insights into structure optimization were screened against the insecticide-resistant, Puerto Rico (PR), strain of and it was discovered that not only did these N-arylamides typically show little resistance, some such as -(2,6-dichloropyridin-4-yl)-2,2,3,3,4,4,4-heptafluorobutanamide (compound ) and 2,2,3,3,4,4,4-heptafluoro--(3,4,5-trifluorophenyl)butanamide (compound ) were actually more potent against the PR mosquitoes. Due to this promising insecticidal activity, five compounds were administered orally to mice to determine acute oral rodent toxicity. All five compounds were found to have mouse oral toxicity LD values well above the minimum safe level as set by the Innovative Vector Control Consortium (50 mg/kg). In addition to the promising biological activity documented here, we report the structure-activity relationship analysis used to guide the derivatization approach taken and to further inform future efforts in the development of N-arylamides as potential resistance-breaking, spatially acting insecticides.