Design, Synthesis, and Insecticidal Activity of Novel Isoxazoline Compounds That Contain Meta-diamides against Fall Armyworm (Spodoptera frugiperda)

Abstract

Fall armyworm (Spodoptera frugiperda) is a major migratory pest around the entire world that causes severe damage to agriculture. We designed and synthesized a series of novel isoxazoline derivatives based on the previously discovered active compound H13 to find new and effective candidates against S. frugiperda. Most of them showed excellent insecticidal activity. In addition, a three-dimensional quantitative structure–activity relationship model was established, and compound F32 was designed and synthesized based on the results. The bioassay result showed that compound F32 exhibited excellent activity against S. frugiperda (LC50 = 3.46 mg/L), which was substantially better than that of the positive control fipronil (LC50 = 78.8 mg/L). Furthermore, an insect γ-aminobutyric acid (GABA) enzyme-linked immunosorbent assay indicated that F32 can upregulate the content of GABA in insects in a manner similar to that of fipronil. Molecular docking showed that the hydrophobic effect and hydrogen-bond interactions are vital factors between the binding of F32 and receptors. All of these results suggest that compound F32 could be employed as a novel isoxazoline lead compound to control S. frugiperda.

Discovery of Novel Isoxazoline Compounds that Incorporate a para-Diamide Moiety as Potential Insecticidal Agents against Fall Armyworm (Spodoptera frugiperda)

“…These results also suggested that hydrogen bond interactions between compounds with GABA receptors could improve the binding affinity while maintaining appropriate hydrophobic interactions. This finding are in accord with our previous results …”

“…Therefore, we constructed a homology modeling of S. frugiperda based on the methods reported earlier . The brief description is as follows.…”

“…The structure–activity relationship (SAR) of known isoxazoline compounds has been reviewed by us earlier, which indicated that introducing polar groups into the third position on the phenyl group could facilitate the insecticidal activity. In our early work, based on this analysis of the SAR, we added the traditional diamide skeleton to the third position region on the phenyl group of the isooxazoline structure and discovered the novel isoxazoline active compound F32 , which has superior insecticidal activity against S. frugiperda in comparison with fipronil targeted in the GABA receptor.…”

Onygenaleosides A–F, 6/5 Bicyclic Ring Skeleton Triterpene Glycosides with Insecticidal Activity from Onygenales sp. YX1425

“…The insecticidal activity against Spodoptera frugiperda was evaluated according to a previous method. − The compounds (10 mg/mL) in DMSO were prepared and further diluted with distilled water containing 1‰ Tween-80 to the concentrations of 62.5, 125, 250, and 500 μg/mL. The fresh corn leaf disks (5 mm × 5 mm) were soaked in the solution of the test reagent 3–5 times.…”

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

“… However, they are approved only in limited countries and are not widely available worldwide. Therefore, further exploration of isoxazolines for the development of efficient insecticides with biosafe for nontarget organisms and environmentally friendly has attracted widespread attention. − …”