Yanjiao Feng , Jialin Cui , Hongyan Wang , Qinyan Tan , Shangzhong Liu , Libing Liu , Li Zhang
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引用次数: 0
Abstract
The ecdysone receptor (EcR/USP) plays a vital role in regulating molting and metamorphosis in insects, rendering it an attractive green target for developing novel insect growth regulators (IGRs). In this study, the ligand pharmacophore model S1&S2 and the Combine active pockets were constructed on the basis of the two different ligand-binding pockets of Lepidoptera EcR. A multi-level virtual screening of the SPECS database was performed, using pesticide-likeness rule and molecular docking, to obtain 13 screening compounds. Then, a novel experimental method was established to evaluate Plutella xylostella EcR/USP-LBD binding to ligand molecules using the Surface Plasmon Resonance (SPR) technique. The binding assays demonstrated that compounds VS-13, VS-16, VS-17, VS-18, and VS-19 exhibited comparable or superior efficacy to the commercial insecticide methoxyfenozide. Notably, VS-13 showed the highest binding activity, with a Kd of 0.2 ± 0.03 μM, similar to Ponesterone A (PonA, Kd = 0.1 ± 0.01 μM). Furthermore, molecular docking studies revealed that, in addition to three important residues (Asn503, Tyr407, and Thr342), Trp525 and Met379 are also key residues in stable the ligand-receptor interactions. These findings provide an effective strategy to design and discovery novel non-ecdysteroid analogs targeting lepidopteran insects.
期刊介绍:
Pesticide Biochemistry and Physiology publishes original scientific articles pertaining to the mode of action of plant protection agents such as insecticides, fungicides, herbicides, and similar compounds, including nonlethal pest control agents, biosynthesis of pheromones, hormones, and plant resistance agents. Manuscripts may include a biochemical, physiological, or molecular study for an understanding of comparative toxicology or selective toxicity of both target and nontarget organisms. Particular interest will be given to studies on the molecular biology of pest control, toxicology, and pesticide resistance.
Research Areas Emphasized Include the Biochemistry and Physiology of:
• Comparative toxicity
• Mode of action
• Pathophysiology
• Plant growth regulators
• Resistance
• Other effects of pesticides on both parasites and hosts.