Rational Design of Insecticidal Isoxazolines Containing Sulfonamide or Sulfinamide Structure as Antagonists of GABA Receptors with Reduced Toxicities to Honeybee and Zebrafish

To develop highly effective, nontarget organism-friendly insecticides based on the isoxazoline scaffold, we rationally designed and synthesized 25 isoxazoline derivatives containing sulfonamides and sulfinamides. Their insecticidal activities against the diamondback moth (Plutella xylostella), fall armyworm (Spodoptera frugiperda), beet armyworm (Spodoptera exigua), and Spodoptera litura Fabricius (S. litura) were evaluated. The trifluoromethyl sulfinamide-containing compound 7w displayed excellent activities with LC50 values being 0.09, 0.84, 0.87, and 0.68 mg/L against P. xylostella, S. frugiperda, S. exigua, and S. litura, respectively, which were superior to fluxametamide (LC50 = 0.09, 1.24, 1.10, and 0.65 mg/L, respectively) and maintained at the same order of magnitude LC50 values as fluralaner (LC50 = 0.02, 0.17, 0.12, and 0.19 mg/L, respectively). Importantly, compound 7w showed a medium toxicity level of acute toxicity to honeybee (LD50 = 2.22 μg/adult), which is significantly lower than the fluralaner (high toxicity level, LD50 = 0.09 μg/adult). Acute toxicity experiments with zebrafish (Danio rerio) indicated that compound 7w was safe with the LC50 value being 42.4 mg/L (low toxicity level). Furthermore, electrophysiological experiments and molecular docking studies preliminarily verified that compound 7w acts on the insect GABA receptor, and the theoretical calculations explained that the sulfinamide structure may play an important role in exhibiting biological activities. The above results suggest that compound 7w could be employed as a potentially highly effective, environmentally friendly insecticide to control multiple agricultural pests

Analysis of variance to assess the impacts of precipitation, CO₂, and their interaction on soil water content, photosynthetic parameters, biomass accumulation and biomass allocation in the grass species <i>L. Chinensis</i>.

<p>Note:Data are significant at <i>P</i><0.05 level (bolded values).</p

Effect of precipitation on biomass of <i>L. Chinensis</i> under two CO₂ concentrations.

<p>Note: Different lower-case letters indicate a significant difference among precipitation levels and different capital letters indicate a significant difference between the two CO₂ levels (<i>P</i><0.05). Low/High precipitation were defined as normal precipitation +/−40%.</p

Effect of precipitation on biomass allocation among plant parts under two CO₂ concentrations for <i>Leymus chinensis</i>.

<p>Different lower-case letters indicate a significant difference among different precipitation levels, and different capital letters indicate a significant difference between the two CO₂ levels (<i>P</i><0.05). LP, P, HP represents low precipitation (−40%), normal precipitation and high precipitation (+40%), respectively.</p

Effect of precipitation on soil water content under two CO₂ concentrations.

<p>LP, P, HP represents low precipitation (−40%), normal precipitation and high precipitation (+40%), respectively. Different letters indicate a significance difference among levels of precipitation (<i>P</i><0.05).</p