Structural Diversity Design, Synthesis, and Insecticidal Activity Analysis of Ester-Containing Isoxazoline Derivatives Acting on the GABA Receptor

Ligand-gated ion channels are essential in living organisms, and sulfonamides have antibacterial effects and can be readily coordinated with metal ions with good biological activity. A series of fluorescent ligand-gated ion channel fused arylpyrazole sulfonamide skeletons (APSn M ) were synthesized based on a one-pot ultrasound strategy promoted by an inorganic base. APSn M had a high fluorescence quantum yield and a large Stokes shift in ethanol solvent. The ligand bonded ions took on a different color from the ligand and can be used as a probe to detect their own residue on plant surfaces. Their hydrophobic parameters and the fluorescence distribution in Chinese cabbage leaves indicated that APSn M significantly increased the phloem mobility of the plant. The insecticidal activity of APS3 Na was higher (LC 50 = 7.2423 μg/mL) than that of fipronil (15.2312 μg/mL) against Plutella xylostella, and the mechanism of high insecticidal activity of APS3 Na was simulated by molecular docking, which confirmed its strong interactions with the GABA and nACh receptors of Plutella xylostella. Analysis of the crystal structure of these ligand-gated ion channels further confirmed the consistency of their structure and biological activity.

Section: Resultsmentioning

confidence: 99%

Section: Fluorescent Ligand-gated Ion Channels (Apsn M ) Enhanced Phl...mentioning

confidence: 91%

Design and One-Pot Ultrasound Synthesis of Inorganic Base-Promoted Fluorescent Ligand-Gated Ion Channel Fused Arylpyrazole Sulfonamide Skeletons to Enhance Phloem Mobility and Insecticidal Activity as GABA and nACh Receptors Inhibitors

Xu,

Wu,

Wan

et al. 2023

“…The molecular structure optimization and minimum energy calculations were performed by the Density Functional Theory (DFT) method of Discovery Studio 2021. Finally, the tested compound’s highest occupied molecular orbital and lowest unoccupied molecular orbital (HOMO and LUMO) and molecular electrostatic potential (MEP) were obtained, plotted, and visualized. − …”

Section: Methodsmentioning

confidence: 99%

Discovery of Pyrazole-5-yl-amide Derivatives Containing Cinnamamide Structural Fragments as Potential Succinate Dehydrogenase Inhibitors

Cheng,

Xu,

Cui

et al. 2023

To promote the development of novel agricultural succinate dehydrogenase inhibitor (SDHI) fungicides, we introduced cinnamamide and nicotinamide structural fragments into the structure of pyrazol-5-yl-amide by carbon chain extension and scaffold hopping, respectively, and synthesized a series of derivatives. The results of the biological activity assays indicated that most of the target compounds exhibited varying degrees of inhibitory activity against the tested fungi. Notably, compounds G22, G28, G34, G38, and G39 exhibited excellent in vitro antifungal activities against Valsa mali with EC 50 values of 0.48, 0.86, 0.57, 0.73, and 0.87 mg/L, respectively, and this result was significantly more potent than boscalid (EC 50 = 2.80 mg/L) and closer to the specialty control drug tebuconazole (EC 50 = 0.30 mg/L). Compounds G22 and G34 also exhibited excellent in vivo protective and curative effects against V. mali at 40 mg/L. The SEM and TEM observations indicated that compounds G22 and G34 may affect normal V. mali mycelial morphology as well as the cellular ultrastructure. Molecular docking analysis results indicated that G22 and boscalid possessed a similar binding mode to that of SDH, and detailed SDH inhibition assays validated the feasibility of the designed compounds as potential SDH inhibitors. Compounds G22 and G3 were selected for theoretical calculations, and the terminal carboxylic acid group of this series of compounds may be a key region influencing the antifungal activity. Furthermore, toxicity tests on Apis mellifera l. revealed that compounds G22 and G34 exhibited low toxicity to A. mellifera l. populations. The above results demonstrated that these series of pyrazole-5-yl-amide derivatives are promising for development as potential low-risk drug-resistance agricultural SDHI fungicides.

“…Insecticidal activities for the title compounds I, II, and the positive control CHL against the third larvae of M. separata and P. xylostella were evaluated using a leaf-dipping method. 29 Insecticidal activities against wild and resistant type S. frugiperda were tested using an artificial diet method. 30 The larvae were considered dead if they did not show an obvious response to light touch with a brush detected 72 h later.…”

Section: Insecticidal Bioassaysmentioning

confidence: 99%

Novel Nitrophenyl Substituted Anthranilic Diamide Derivatives: Design, Synthesis, Selectivity, and Antiresistance

Sun,

Zhang,

Zhao

et al. 2023

Diamide insecticides have gained popularity due to their high efficacy and low toxicity to nontarget organisms. However, diamide-associated resistance has emerged recently, causing a significant reduction in their potency, thereby hindering sustainable agricultural development. Here, we explored novel diamide insecticide analogs and, using a structure-based approach, rationally designed and synthesized 28 nitrophenyl substituted anthranilic diamides. Most of the compounds showed moderate to good activity against Mythimna separata, Plutella xylostella, and Spodoptera frugiperda. Among them, compounds Ia and Im showed extraordinarily high activity and their mode of action was verified on isolated neurons. Additionally, Im exhibited over 10-fold greater potency than chlorantraniliprole in a HEK293 cell line stably expressing S. frugiperda ryanodine receptors (Sf RyRs) containing the resistance mutations, G4891E and I4734M. The binding modes of Im in the Sf RyRs were predicted using in silico molecular docking analysis. Our novel nitrophenyl substituted anthranilic diamide derivatives provide valuable insights for the design of insecticidal RyR-targeting compounds to effectively control both wild type and diamide insecticide-resistant lepidopteran pests.