College of Agriculture, Liaocheng University, Liaocheng, P. R. China.
College of Chemical Engineering and Materials Science, Zhejiang University of Technology, Hangzhou, P. R. China.
Pest Manag Sci. 2020 Jul;76(7):2368-2378. doi: 10.1002/ps.5773. Epub 2020 Feb 20.
Succinate dehydrogenase (SDH) has been identified as one of the most significant targets for fungicide discovery. To date, 23 commercial SDH inhibitor (SDHI) fungicides have been approved for plant protection since the first launch of carboxin in 1966, and extensively applied to combat destructive plant fungi.
In this project, 20 novel pyridine sulfide derivatives containing SDH-based heterocyclic amide fungicide were designed, synthesized, and characterized by proton nuclear magnetic resonance ( H-NMR), carbon-13 ( C)-NMR and high-resolution mass spectrometry (HRMS). In vitro fungicidal activity experiment, the target compound I-1 displayed excellent inhibitory rates against the common agricultural pathogens with half maximal effective concentration (EC ) values of 5.2 to 39.8 μg mL . The in vivo fungicidal activities demonstrated that the compound I-1 could effectively prevent Botrytis cinerea from infecting tomato and cucumber leaves with the preventative rates of 67% and 50%. The mitochondrial membrane potential detection, SDH enzyme assay and the molecular docking simulation revealed that the mechanism of action of the compound I-1 and the relevant interactions with the target enzyme may be similar to those of the control fluopyram.
The biological activity screening and validation of mechanism of action indicated that the compound I-1 could be identified as a potential SDH inhibitor for further study. © 2020 Society of Chemical Industry.
琥珀酸脱氢酶（SDH）已被确定为杀菌剂发现的最重要靶标之一。自 1966 年第一个 carbothrax 上市以来，目前已有 23 种商业 SDH 抑制剂（SDHI）杀菌剂获得批准用于植物保护，并广泛用于防治破坏性植物真菌。
在本项目中，设计、合成并通过质子核磁共振（ H-NMR）、碳-13（ C）-NMR 和高分辨率质谱（HRMS）对 20 种新型吡啶硫化物衍生物进行了表征，这些衍生物含有基于 SDH 的杂环酰胺类杀菌剂。体外杀菌活性实验表明，目标化合物 I-1 对常见农业病原菌具有优异的抑制活性，半数最大有效浓度（EC ）值为 5.2 至 39.8μg mL 。体内杀菌活性表明，化合物 I-1 能有效防止灰葡萄孢侵染番茄和黄瓜叶片，预防率分别为 67%和 50%。线粒体膜电位检测、SDH 酶活性测定和分子对接模拟表明，化合物 I-1 的作用机制及其与靶酶的相互作用可能与对照药剂 fluopyram 相似。
生物活性筛选和作用机制验证表明，化合物 I-1 可被鉴定为进一步研究的潜在 SDH 抑制剂。 © 2020 英国化学学会。
