Target-Based Design, Synthesis, and Biological Evaluation of Novel 1,2,4-Triazolone Derivatives as Potential nAChR Modulators

Rational Design of Triazinone Derivatives with Low Bee Toxicity Based on the Binding Mechanism of Neonicotinoids to Apis mellifera

“…Naturally, the premise of designing low bee toxicity compounds is to ensure that they have good insecticidal activity. In our previous work, three crucial binding features of commercial neonicotinoids with receptors were identified, which could inform the design of target compounds (Figure S6), where a water-bridged hydrogen-bonding network and π-CH/π–π stacking interactions formed by pyridine. Based on this, pyridine was retained, and the central part was occupied by a heterocycle containing nitrogen or oxygen atoms.…”

“…Therefore, compounds were designed by adding the functional triazinone fragment to the central part (red circle) of the model (Figure A). As shown in Figure B, the binding mode of compound 5a was similar to that of the commercial neonicotinoids . The nitro atom of pyridine showed a strong interaction to a water molecule with a distance of 2.2 Å and then formation of interactions with ILE106 and ILE118 at 1.8 and 2.1 Å, respectively.…”

“…The insecticidal efficacy of compounds against Aphis glycines and Myzus persicae was evaluated using a leaf-dipping methodology outlined in the literature . Compounds were initially dissolved in dimethyl sulfoxide (DMSO) and then diluted to the required concentrations with a 0.5% Tween-80 aqueous solution.…”

Computational Modeling Oriented Substructure Splicing Application in the Identification of Thiazolidine Derivatives as Potential Low Honeybee Toxic Neonicotinoids

“…Acetylcholine binding proteins (AChBPs) have been widely recognized as good structural surrogate for the ligand binding domain of nAChRs. The cocrystal structures of double mutant L. stagnalis AChBP ( Ls- AChBP) with neonicotinoid insecticides provide valuable clues to understand the molecular recognition between neonicotinoids and nAChRs. − Neonicotinoid insecticide flupyradifurone bound Ls- AChBP (PDB ID: 7PDB) was selected as receptor, and the docking grid was set around flupyradifurone with a size of 10 Å. Molecular docking was performed using the Glide module in Maestro 10.2 (Schrödinger, LLC, 2015) in standard precision. The docking poses with superior docking scores were selected for binding mode analysis.…”

Recent Research Progress in Oxime Insecticides and Perspectives for the Future

“…Both triazole and isoxazoline are nitrogen-containing heterocycles, which exhibit diverse biological activities and are commonly used as antifungal agents − and insecticides . Shi and his team reported a series of 1,2,3-triazol oxime derivatives, which exhibited promising insecticidal efficacy, particularly against aphids .…”