Inhibition of Glucosinolate Sulfatases to Combat <i>Plutella xylostella</i>: Development of Novel Phenylcarboxamide Derivatives for Plant-Integrated Pest Management

Glucosinolates in cruciferous plants are hydrolyzed by myrosinase to produce toxic isothiocyanates (ITCs). However, <i>Plutella xylostella</i> (<i>P. xylostella</i>), one of the top 10 global agricultural pests, utilizes glucosinolate sulfatases (GSSs) in its gut to convert glucosinolates into nontoxic desulfo-glucosinolates, thereby effectively avoiding the toxicity of ITCs. This study investigates the potential of inhibiting GSSs. Among 16 synthesized phenylcarboxamide derivatives, compound <b>1n</b> exhibited strong inhibitory activity against GSS1 (59.72%) and GSS2 (88.47%), key enzymes involved in glucosinolate desulfation in <i>P. xylostella</i>, leading to toxic ITC accumulation and disrupted detoxification. This resulted in an approximately 30% reduction in larval weight, at a concentration of 100 mg/L, the mortality rate reached 96%. Importantly, in the absence of glucosinolates, these inhibitors showed no direct toxicity to the insect, indicating that their action relies on interaction with the plant's chemical defense system. These findings provide strong evidence supporting the development of GSSs inhibitions as more specific and selective insecticide, offering a promising alternative to conventional chemical pesticides.