基于结构的合理设计与合成靶向八氢番茄红素脱饱和酶的哒嗪酮类除草剂
Structure-Based Rational Design and Synthesis of Pyridazinone Herbicides Targeting Phytoene Desaturase.
摘要(中文译文)
除草剂的应用对保障粮食安全起着至关重要的作用。然而，长期过量使用除草剂会带来一系列不良影响。因此，开发创新且可持续的除草剂十分必要。本研究采用基于结构的药物设计策略，设计并合成了一系列靶向八氢番茄红素脱氢酶（PDS）的哒嗪酮类衍生物。生物测定表明，在150 g a.i./ha剂量下，无论苗后还是苗前施用，化合物16c对马齿苋（P.o.）的除草活性（100%、85%）均强于氟啶酮（NRF，60%、45%），同时对非靶标生物表现出更高的安全性。同时，15-顺式-八氢番茄红素、类胡萝卜素和叶绿素水平的变化表明，16c能有效抑制PDS活性。分子动力学模拟和结合作用试验证实，Arg195是16c与聚球藻PDS（SynPDS）相互作用的关键残基。因此，16c有望开发为一种高效的除草剂PDS抑制剂。
Abstract
The application of herbicides plays a critical role in ensuring food security. However, the long-term overuse of herbicides can lead to a range of adverse effects. Therefore, it is essential to develop innovative and sustainable herbicides. A series of pyridazinone derivatives targeting phytoene desaturase (PDS) were designed and synthesized by using a structure-based drug design strategy. A bioassay showed that 16c (100%, 85%) exhibited stronger herbicidal activity against portulaca oleracea (P.o.) than that of norflurazon (NRF, 60%, 45%) in both post- and pre-emergence applications at a dosage of 150 g a.i./ha, while also showing greater safety to nontarget organisms. Meanwhile, levels of 15-cis-phytoene, carotenoids, and chlorophyll revealed that 16c effectively inhibited PDS activity. Molecular dynamics simulations and binding action assays confirmed that Arg195 is a key residue for the interaction between 16c and Synechococcus PDS (SynPDS). Therefore, 16c could be developed as a potent PDS inhibitor for herbicides.
如何引用
AMA
Chao Chen, Yan Li, Wei Zhang, Xiuhai Gan. Structure-Based Rational Design and Synthesis of Pyridazinone Herbicides Targeting Phytoene Desaturase.. Journal of agricultural and food chemistry. 2026; doi:10.1021/acs.jafc.6c01243.
APA
Chao Chen, Yan Li, Wei Zhang, Xiuhai Gan (2026). Structure-Based Rational Design and Synthesis of Pyridazinone Herbicides Targeting Phytoene Desaturase.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c01243
GB/T 7714
Chao Chen, Yan Li, Wei Zhang, Xiuhai Gan. Structure-Based Rational Design and Synthesis of Pyridazinone Herbicides Targeting Phytoene Desaturase.[J]. Journal of agricultural and food chemistry, 2026 doi:10.1021/acs.jafc.6c01243.
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