Discovery of the Chlorinated and Ammoniated Derivatives of Vanillin as Potential Insecticidal Candidates Targeting V-ATPase: Structure-Based Virtual Screening, Synthesis, and Bioassay,Journal of Agricultural and Food Chemistry

当前位置： X-MOL 学术 › J. Agric. Food Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Discovery of the Chlorinated and Ammoniated Derivatives of Vanillin as Potential Insecticidal Candidates Targeting V-ATPase: Structure-Based Virtual Screening, Synthesis, and Bioassay
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-09-11 , DOI: 10.1021/acs.jafc.4c05174
Bo Lv _{1,

2} , Xianxia Zhang _{1,

2} , Yu Wang _{1,

2} , Wenjun Wu ₁ , Ding Li _{1,

3} , Zhaonong Hu _{1,

2}

Affiliation

Vacuolar-type H⁺-ATPases (V-ATPases) play a crucial role in the life cycle of agricultural pests and represent a promising target for the development of novel insecticides. In this study, S18, a derivative of vanillin acquired from Specs database using a structure-based virtual screening methodology, was first identified as a V-ATPase inhibitor. It binds to subunit A of the enzyme with a K_d of 1 nM and exhibits insecticidal activity against M. separata. Subsequently, using S18 as the lead compound, a new series of vanillin derivatives were rationally designed and efficiently synthesized. and their biological activities were assessed. Among them, compound 3b-03 showed the strongest insecticidal activity against M. separata by effectively targeting the V-ATPase subunit A with K_d of 0.803 μM. Isothermal titration calorimetric measurements and docking results provided insights into its interaction with subunit A of V-ATPase, which could facilitate future research aimed at the development of novel chemical insecticides.

中文翻译：

发现香草醛的氯化和氨化衍生物作为针对 V-ATP 酶的潜在杀虫剂候选物：基于结构的虚拟筛选、合成和生物测定

液泡型H ⁺ -ATP酶（V-ATP酶）在农业害虫的生命周期中发挥着至关重要的作用，是新型杀虫剂开发的一个有前景的目标。在这项研究中， S18是一种香草醛衍生物，使用基于结构的虚拟筛选方法从 Specs 数据库中获得，首次被鉴定为 V-ATP 酶抑制剂。它与该酶的 A 亚基结合， K _d为 1 nM，并对M. separata表现出杀虫活性。随后以S18为先导化合物，合理设计并高效合成了一系列新的香兰素衍生物。并评估了它们的生物活性。其中，化合物3b-03通过有效靶向V-ATP酶A亚基，对M. separata表现出最强的杀虫活性， K _d为0.803 μM。等温滴定量热测量和对接结果提供了对其与 V-ATP 酶 A 亚基相互作用的深入了解，这可能有助于未来旨在开发新型化学杀虫剂的研究。

更新日期：2024-09-11

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南