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

Abstract

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 <b>7</b> showed 69.7% lethality against <i>Aedes albopictus</i> (<i>A. albopictus</i>) at the concentration of 0.125 mg/L. Compounds <b>7</b>, <b>7g</b>, <b>8d,</b> and <b>10j</b> showed superior insecticidal activity for the control of <i>Plutella xylostella</i> (<i>P. xylostella</i>). Notably, compound <b>7</b> showed similar insecticidal activity against <i>Aphis craccivora</i> (<i>A. craccivora</i>) compared with fipronil. Potential surface calculation and molecular docking suggested that different lipophilicity and binding models to the <i>Musca domestica</i> (<i>M. domestica</i>) gamma-aminobutyric acid receptors may be responsible for the decreased activity of the tested derivatives. Toxicity tests indicated that compound <b>8d</b> (LC₅₀ = 14.28 mg/L) induced obviously 14-fold lower toxicity than fipronil (LC₅₀ = 1.05 mg/L) on embryonic-juvenile zebrafish development.