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

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 (-, -, and -). The postemergence application assay demonstrated that and 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 and PDS (PDS). The HPLC analysis confirmed that at 750 g a.i./ha caused significant phytoene accumulation in 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.