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

Abstract

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.

Design and Enantioselective Synthesis of Chiral Pyranone Fused Indole Derivatives with Antibacterial Activities against Xanthomonas oryzae pv oryzae for Protection of Rice

“…Rice is the world’s most vital crop, serving as the primary calorie source for more than half of the global population. − Rice bacterial leaf blight caused by Xanthomonas oryzae pv oryzae ( Xoo ), a rod-shaped, Gram-negative bacterium, poses a significant threat to rice production − that has led to crop yield decreases ranging from 10% to 50% and enormous economic losses in agriculture every year. − The transmission of rice bacterial leaf blight primarily occurs through lesions on leaf tips, margins, and wounds, giving rise to symptoms such as leaf wilt, necrosis, and other abnormal growth patterns. , Among various control measures, chemical pesticides are pivotal for the management of the rice bacterial leaf blight disease in crop protection, − such as bismerthiazol (BT) and thiodiazole copper (TC), which are widely adopted as bactericides in China to control this disease. Unfortunately, the efficacy of these agrochemicals falls short of expectations.…”