Discovery of a Novel Class of Acylthiourea-Containing Isoxazoline Insecticides against Plutella xylostella

Abstract

Isoxazoline structures are widely found in natural products and are rich in biological activities. This study discloses the development of a series of novel isoxazoline derivatives by introducing acylthiourea fragments to access insecticidal activity. All synthetic compounds were examined for their insecticidal activity against Plutella xylostella, with results showing moderate to strong activity. Based on this, the structure–activity relationship analysis was carried out via the constructed three-dimensional quantitative structure–activity relationship model to further guide the structure optimization, resulting in the optimal compound 32. The LC50 of compound 32 against Plutella xylostella was 0.26 mg/L, demonstrating better activity than the positive control, ethiprole (LC50 = 3.81 mg/L), avermectin (LC50 = 12.32 mg/L), and compounds 1–31. The insect GABA enzyme-linked immunosorbent assay demonstrated that compound 32 might act on the insect GABA receptor, and the molecular docking assay further illustrated the mode of action of compound 32 with the GABA receptor. In addition, the proteomics analysis indicated that the action of compound 32 on Plutella xylostella was multi-pathway.

Recent Research Progress in Oxime Insecticides and Perspectives for the Future

“…In addition, studies on the insecticidal activity of isoxazolines reported in recent years have confirmed that isoxazoline compounds can significantly inhibit the GABA receptors of insects. For example, Hu and Song et al revealed that isoxazoline compounds 98 and 99 (Figure ) may affect the insect’s nervous system by acting on the GABA receptors. − Our research group also confirmed compound 100 (Figure ) as an inhibitor of insect GABA receptor via proteomics and electrophysiological experiments …”

“…The team successfully isolated two enantiomers of compound 99 via high performance liquid chromatography, wherein the cis -configuration exhibited an insecticidal activity that was 44 times higher than that of the trans -configuration. However, the introduction of large groups resulted in a decrease in insecticidal activity of the compound. , In addition, our research group synthesized a series of isoxazoline molecules containing diacylhydrazine based on the core framework of fluralaner. Among them, compound 100 exhibited the LC 50 value of 0.37 μg/mL against P. xylostella and was found to be an inhibitor of GABA receptor in insects via proteomic and electrophysiological experiments .…”

“…However, the introduction of large groups resulted in a decrease in insecticidal activity of the compound. 94,95 In addition, our research group synthesized a series of isoxazoline molecules containing diacylhydrazine based on the core framework of fluralaner. Among them, compound 100 exhibited the LC 50 value of 0.37 μg/mL against P. xylostella and was found to be an inhibitor of GABA receptor in insects via proteomic and electrophysiological experiments.…”

Exploring the latest trends in chemistry, structure, coordination, and diverse applications of 1-acyl-3-substituted thioureas: a comprehensive review

“…86). 138 A series of novel acyl thiourea derivatives (161a-s) was evaluated for their mosquito larvicidal activity against C. quinquefasciatus and A. aegypti 3rd instar larvae. Compound (161l) showed the highest larvicidal activity with LC 50 values of 0.0044 mM and 0.0070 mM, and LC 90 values of 0.0058 mM and 0.0103 mM against C. quinquefasciatus and A. aegypti, respectively.…”

Metabolite profiling and in-silico studies show multiple effects of insecticidal actinobacterium on Spodoptera littoralis

“…WHUA03267 and St. sp. WHUA03072 21 . Additionally, molecular docking was used to assess insecticidal activity against Plutella xylostella and illustrate the identified compound action with the GABA (γ-aminobutyric acid) receptor 21 .…”