Phytoene desaturase (PDS) is a key rate-limiting enzyme in the carotenoid biosynthesis pathway. Although commercial PDS inhibitors have been developed for decades, it remains necessary to develop novel PDS inhibitors with higher bioactivity. In this work, we used the scaffold hopping and linker modification approaches to design and synthesize a series of compounds (7a–7o, 8a–8l, and 14a–14d). The postemergence application assay demonstrated that 8e and 7e separately showed the best herbicidal activity at 750 g a.i./ha and lower doses (187.5 g, 375g a.i./ha) without no significant toxicity to maize and wheat. The surface plasmon resonance revealed strong binding affinity between 7e and Synechococcus PDS (SynPDS). The HPLC analysis confirmed that 8e at 750 g a.i./ha caused significant phytoene accumulation in Arabidopsis seedlings. This work demonstrates the efficacy of structure-guided optimization through scaffold hopping and linker modification to design potent PDS inhibitors with enhanced bioactivity and crop safety.

中文翻译：

---

通过支架跳跃和接头修饰发现新型（5-巯基-4-苯基-4H-1,2,4-三唑-3-基）甲基苯基氨基甲酸酯作为有效的八氢番茄红素去饱和酶抑制剂


八氢番茄红素去饱和酶（PDS）是类胡萝卜素生物合成途径中的关键限速酶。尽管商业PDS抑制剂已经开发了几十年，但仍然有必要开发具有更高生物活性的新型PDS抑制剂。在这项工作中，我们使用支架跳跃和接头修饰方法来设计和合成一系列化合物（ 7a – 7o 、 8a – 8l和14a – 14d ）。芽后施用试验表明， 8e和7e分别在750 g ai/ha和较低剂量（187.5 g、375g ai/ha）时显示出最佳除草活性，对玉米和小麦没有明显毒性。表面等离子体共振显示7e和聚球藻PDS ( Syn PDS)之间有很强的结合亲和力。 HPLC 分析证实，750 g ai/ha 的8e引起拟南芥幼苗中显着的八氢番茄红素积累。这项工作证明了通过支架跳跃和接头修饰进行结构引导优化的有效性，以设计具有增强生物活性和作物安全性的有效 PDS 抑制剂。