Discovery of Novel (5-Mercapto-4-phenyl-4 H -1,2,4-triazol-3-yl)methyl Phenyl Carbamate as a Potent Phytoene Desaturase Inhibitor through Scaffold Hopping and Linker Modification

作者：Di Zhang, Chunxue Wang, Yichi Zhang, Zhilei Yu, Zeyu Hong, Ding Jia, Dejun Ma, Yu‐Cheng Gu, Han Xu, Zhen Xi · 发表于：Journal of Agricultural and Food Chemistry · 年份：2024 · DOI：10.1021/acs.jafc.4c05989 · 被引用次数：6 · 研究领域：Antioxidant Activity and Oxidative Stress、Plant biochemistry and biosynthesis、Retinoids in leukemia and cellular processes

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 ( Syn PDS). 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.