Ligand-based virtual screening, molecular docking, and molecular dynamics of eugenol analogs as potential acetylcholinesterase inhibitors with biological activity against Spodoptera frugiperda,Molecular Diversity

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Ligand-based virtual screening, molecular docking, and molecular dynamics of eugenol analogs as potential acetylcholinesterase inhibitors with biological activity against Spodoptera frugiperda
Molecular Diversity ( IF 3.9 ) Pub Date : 2021-09-16 , DOI: 10.1007/s11030-021-10312-5
Domingo Méndez-Álvarez ₁ , Verónica Herrera-Mayorga ₂ , Alfredo Juárez-Saldivar ₁ , Alma D Paz-González ₁ , Eyra Ortiz-Pérez ₁ , Debasish Bandyopadhyay ₃ , Horacio Pérez-Sánchez ₄ , Gildardo Rivera ₁

Affiliation

The development of new, more selective, environmental-friendly insecticide alternatives is in high demand for the control of Spodoptera frugiperda (S. frugiperda). The major objective of this work was to search for new potential S. frugiperda acetylcholinesterase (AChE) inhibitors. A ligand-based virtual screening was initially carried out considering six scaffolds derived from eugenol and the ZINC15, PubChem, and MolPort databases. Subsequently, molecular docking analysis of the selected compounds on the active site and a second region (determined by blind molecular docking) of the AChE of S. frugiperda was performed. Molecular dynamics and Molecular Mechanics Poisson–Boltzmann Surface Area analyses were also applied to improve the docking results. Finally, three new eugenol analogs were evaluated in vitro against S. frugiperda larvae. The virtual screening identified 1609 compounds from the chemical libraries. Control compounds were selected from the interaction fingerprint by molecular docking. Only three new eugenol analogs (1, 3, and 4) were stable at 50 ns by molecular dynamics. Compounds 1 and 4 had the best biological activity by diet (LC₅₀ = 0.042 mg/mL) and by topical route (LC₅₀ = 0.027 mg/mL), respectively. At least three new eugenol derivatives possessed good-to-excellent insecticidal activity against S. frugiperda.

Graphic abstract

中文翻译：

丁香酚类似物的基于配体的虚拟筛选、分子对接和分子动力学作为潜在的乙酰胆碱酯酶抑制剂，对草地贪夜蛾具有生物活性

对于防治草地贪夜蛾（S. frugiperda），迫切需要开发新的、选择性更高、环境友好的杀虫剂替代品。这项工作的主要目的是寻找新的潜在S. frugiperda乙酰胆碱酯酶 (AChE) 抑制剂。最初进行基于配体的虚拟筛选，考虑来自丁香酚和 ZINC15、PubChem 和 MolPort 数据库的六个支架。随后，对所选化合物在S. frugiperda的 AChE 的活性位点和第二个区域（由盲分子对接确定）进行分子对接分析进行了。还应用分子动力学和分子力学泊松-玻尔兹曼表面积分析来改善对接结果。最后，三种新的丁香酚类似物在体外针对S. frugiperda幼虫进行了评估。虚拟筛选从化学库中识别出 1609 种化合物。通过分子对接从相互作用指纹中选择对照化合物。只有三种新的丁香酚类似物（1、3 和 4）通过分子动力学在 50 ns 时稳定。_{化合物 1 和 4 分别通过饮食 (LC 50} = 0.042 mg/mL) 和局部途径 (LC ₅₀ = 0.027 mg/mL)具有最佳生物活性。至少三种新的丁香酚衍生物对S. frugiperda具有良好至优异的杀虫活性。

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更新日期：2021-09-16

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