Design, synthesis, and insecticidal activities of novel thioether derivatives

Abstract

Mosquitoes are significant vectors of diseases which cause tens of thousands of deaths annually and impose heavy treatment costs on affected regions. Although insecticides have been effective in managing pest damage, their widespread and continuous use has led to the emergence of resistance, presenting a major challenge in pest control. To address this issue, the design of novel insecticides is crucial. A series of novel thioether compounds were synthesized and characterized via a scaffold hopping strategy and their insecticidal activity against both larvae and adult mosquitoes of Armigeres subalbatus, as well as against Brevicoryne brassicae and Pieris rapae Linn were evaluated. All target compounds exhibited excellent insecticidal activity. The insecticidal mechanisms were investigated through Ellman’s method and molecular docking studies. Additionally, DFT calculations were used to analyze why compound A7 (LC₅₀=0.0155 mg/L) showed less insecticidal activity compared to the positive control, cypermethrin (LC₅₀=0.0145 mg/L) and higher insecticidal activity compared to dichlorvos (LC₅₀=0.0469 mg/L). A 3D-QSAR model was developed to predict the efficacy of this class of compounds and the ADME properties revealed good lipophilicity and well-predicted oral bioavailability. The findings of this study are expected to contribute to the development of more effective and environmentally friendly agricultural chemicals, addressing the issue of pest resistance.