Discovery, synthesis, and acaricidal activity evaluation of deep learning-assisted diphenyloxazoline thiosulfonate derivatives.

BACKGROUND

Phytophagous mites are widespread agricultural pests. Under persistent selection pressure from commercial acaricides, Tetranychus cinnabarinus has developed resistance to multiple acaricidal agents, reducing the control efficacy of conventional pesticides. It is therefore imperative to develop novel high-efficiency candidate acaricidal compounds.

RESULTS

In this study, the diphenyloxazoline was selected the core scaffold. Lead compound 7a was obtained via deep learning-assisted molecular design. Based on this core scaffold, a series of thiosulfonate derivatives were further designed and synthesized. Bioassay results revealed that 7d exhibited prominent ovicidal activity against Tetranychus cinnabarinus, with an LC50 value of 0.14 mg/L, outperforming the positive control etoxazole (LC50 = 0.55 mg/L). Moreover, 7d inhibited oviposition in adult mites, displayed low toxicity toward non-target organisms, and demonstrated promising antibacterial activity. Preliminary mechanistic investigations implied that chitin synthase 1 is the potential molecular target of this compound.

CONCLUSIONS

Optimized thiosulfonate 7d exhibits excellent ovicidal activity against T. cinnabarinus, with favorable biosafety and antibacterial activity, and is expected to be developed as a green and high-efficiency acaricide. This work provides key theoretical support and technical guidance for developing new acaricides. © 2026 Society of Chemical Industry.