Yu Wen-Qing, Zhao Li-Xia, Bian Ying, Zhang Pan-Xiu, Jia Ling, Zhao Dong-Mei, Fu Ying, Ye Fei
Department of Chemistry, College of Arts and Sciences, Northeast Agricultural University, Harbin 150030, China.
School of Food Engineering, East University of Heilongjiang, Harbin 150076, China.
J Agric Food Chem. 2025 Feb 12;73(6):3341-3352. doi: 10.1021/acs.jafc.4c07027. Epub 2025 Feb 4.
Mesosulfuron-methyl, an acetolactate synthase (ALS) inhibitor primarily applied to wheat and rye, can injure or even kill wheat crops. Herbicide safeners can improve the herbicide resistance of crops without reducing the herbicidal effect on targeted weed species. Herein, we present a series of pyrazole purine derivatives with the primary structure of the natural product cytokinin and commercialized safener mefenpyridyl, designed using the pharmacophore recombination method. The title compounds were synthesized and characterized using infrared spectroscopy, H and C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. A bioactivity assay proved that most of the target compounds can reduce the wheat phytotoxicity of mesosulfuron-methyl. Measurements of chlorophyll and glutathione contents, along with other enzyme activity assays, confirmed that compounds and exhibit higher safety activities compared with the mefenpyr-diethyl safener. Molecular structure comparisons demonstrated that is more readily absorbed and disseminated through the crop than the commercialized safener mefenpyr-diethyl. Molecular docking models and molecular dynamics simulations elucidated the protective mechanism of safeners; specifically, compound competitively binds to the ALS active site with mesosulfuron-methyl. The current study reveals the potential of pyrazole purine derivatives in the future discovery of novel herbicide safeners.
甲基二磺隆是一种主要用于小麦和黑麦的乙酰乳酸合成酶（ALS）抑制剂，会损害甚至杀死小麦作物。除草剂安全剂可提高作物对除草剂的抗性，同时不降低对目标杂草物种的除草效果。在此，我们展示了一系列具有天然产物细胞分裂素和商业化安全剂吡唑解草酯主要结构的吡唑嘌呤衍生物，采用药效团重组方法设计而成。通过红外光谱、氢和碳核磁共振光谱以及高分辨率质谱对标题化合物进行了合成与表征。生物活性测定证明，大多数目标化合物可降低甲基二磺隆对小麦的植物毒性。叶绿素和谷胱甘肽含量的测定以及其他酶活性测定证实，与解草酯安全剂相比，化合物 和 表现出更高的安全活性。分子结构比较表明， 比商业化安全剂解草酯更容易被作物吸收和传播。分子对接模型和分子动力学模拟阐明了安全剂的保护机制；具体而言，化合物 与甲基二磺隆竞争性结合ALS活性位点。当前研究揭示了吡唑嘌呤衍生物在未来新型除草剂安全剂发现中的潜力。
