Department of Applied Chemistry, College of Arts and Sciences, Northeast Agricultural University, Harbin, China.
Pest Manag Sci. 2021 Apr;77(4):1724-1738. doi: 10.1002/ps.6193. Epub 2020 Dec 9.
Isoxaflutole (IXF), as a kind of 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has been widely used in many kinds of plants. IXF can cause injury in corn including leaf and stem bleaching, plant height reduction or stunting, and reduced crop stand. Safeners are co-applied with herbicides to protect crops without compromising weed control efficacy. With the ultimate goal of addressing Zea mays injury caused by IXF, a series of novel substituted dichloroacetylphenyl sulfonamide derivatives was designed on the basis of scaffold hopping and active substructure splicing.
A total of 35 compounds were synthesized via acylation reactions. All the compounds were characterized by infrared (IR), proton and carbon-13 nuclear magnetic resonance ( H-NMR and C-NMR), and high-resolution mass spectrometry (HRMS). The configuration of compound II-1 was confirmed by single crystal X-ray diffraction. The bioassay results showed that all the title compounds displayed remarkable protection against IXF via improved content of carotenoid. Especially compound II-1 which possessed better glutathione transferases (GSTs) activity and carotenoid content than the contrast safener cyprosulfamide (CSA). All the satisfied parameters suggested that the Comparative Molecular Field Analysis (CoMFA) model was reliable and stable [with a cross-validated coefficient (q ) = 0.527, r = 0.995, r = 0.931]. The molecular docking simulation indicated that the compound II-1 and CSA could compete with diketonitrile (DKN) at the active site of HPPD, which is a hydrolyzed product of IXF in plants, causing the herbicide to be ineffective.
The present work revealed that the compound II-1 deserves further attention as the candidate structure of safeners. © 2020 Society of Chemical Industry.
异噁唑草酮（IXF）作为一种 4-羟基苯基丙酮酸双加氧酶（HPPD）抑制剂，已广泛应用于多种植物。异噁唑草酮可导致玉米叶片和茎变白、植株变矮或矮化、作物倒伏等损伤。安全剂与除草剂一起使用可保护作物，而不影响杂草防治效果。本研究旨在解决玉米因异噁唑草酮而受到的伤害，以支架跳跃和活性亚结构拼接为基础，设计了一系列新型取代二氯乙酰基苯基磺酰胺衍生物。
通过酰化反应合成了 35 种化合物。所有化合物均通过红外（IR）、质子和碳-13 核磁共振（H-NMR 和 C-NMR）以及高分辨率质谱（HRMS）进行了表征。通过单晶 X 射线衍射确定了化合物 II-1 的构型。生物测定结果表明，所有标题化合物均通过提高类胡萝卜素含量对异噁唑草酮表现出显著的保护作用。特别是化合物 II-1，其谷胱甘肽转移酶（GSTs）活性和类胡萝卜素含量均优于对照安全剂环丙磺酰胺（CSA）。所有满意的参数表明比较分子场分析（CoMFA）模型是可靠和稳定的[交叉验证系数（q）= 0.527，r = 0.995，r = 0.931]。分子对接模拟表明，化合物 II-1 和 CSA 可以与二酮腈（DKN）竞争 HPPD 的活性位点，二酮腈是植物中异噁唑草酮的水解产物，从而使除草剂无效。
本研究表明，化合物 II-1 值得进一步关注，可作为安全剂的候选结构。 © 2020 英国化学学会。
