Design, Synthesis, and Insecticidal Activities of Novel Sulfone Derivatives

Abstract

The escalating global population and the resulting increase in food demand have been met with growing challenges from pest infestations, particularly lepidopteran pests, which significantly damage crops. Traditional chemical insecticides face issues such as the development of resistance and environmental harm. Therefore, there is an urgent need for the development of novel insecticides. Sulfone compounds, widely recognized for their utility in medicinal chemistry, have demonstrated potential in enhancing insecticidal efficacy while mitigating environmental impacts. In this study, we explored the design and synthesis of a novel series of sulfone compounds through scaffold hopping strategy and the principle of bioelectronics with the aim of improving insecticidal efficacy against key pests such as Spodoptera litura, Spodoptera frugiperda, and Spodoptera exigua. After evaluating the larvicidal activities, compounds W-27 (LC₅₀ = 0.1205 mg/L) and W-29 (LC₅₀ = 0.1262 mg/L) have emerged as standout performers, exhibiting outstanding larvicidal activity that not only meets but exceeds the potency of the positive control fluralaner (LC₅₀ = 0.1862 mg/L). Structure-activity relationship (SAR) analysis and molecular docking studies were conducted to explore the mechanisms underlying their activity. Additionally, a 3D-QSAR model was developed to predict the insecticidal potency of novel compounds. Toxicity testing on nontarget organisms, such as Solanum lycopersicum and Danio rerio, further confirmed the environmental safety of these compounds. This study paves the way for the development of a new class of agrochemicals, offering novel scaffolds for future pest control applications.

Keywords: insecticidal activity; molecular docking; novel insecticides; sulfone compounds.