Design, Synthesis, and Bioactivity of Trifluoroethylthio-Substituted Phenylpyrazole Derivatives.

As the first marketed phenylpyrazole insecticide, fipronil exhibited remarkable broad-spectrum insecticidal activity. However, it poses a significant threat to aquatic organisms and bees due to its high toxicity. Herein, 35 phenylpyrazole derivatives containing a trifluoroethylthio group on the 4 position of the pyrazole ring were designed and synthesized. The predicted physicochemical properties of all of the compounds were within a reasonable range. The biological assay results revealed that compound 7 showed 69.7% lethality against Aedes albopictus ( A. albopictus ) at the concentration of 0.125 mg/L. Compounds 7 , 7g , 8d, and 10j showed superior insecticidal activity for the control of Plutella xylostella ( P. xylostella ). Notably, compound 7 showed similar insecticidal activity against Aphis craccivora ( A. craccivora ) compared with fipronil. Potential surface calculation and molecular docking suggested that different lipophilicity and binding models to the Musca domestica ( M. domestica ) gamma-aminobutyric acid receptors may be responsible for the decreased activity of the tested derivatives. Toxicity tests indicated that compound 8d (LC ₅₀ = 14.28 mg/L) induced obviously 14-fold lower toxicity than fipronil (LC ₅₀ = 1.05 mg/L) on embryonic-juvenile zebrafish development.