Discovery of Novel Pyrazole Acyl Thiourea Skeleton Analogue as Potential Herbicide Candidates.

To discover novel transketolase (TKL, EC 2.2.1.1) inhibitors with potential herbicidal applications, a series of pyrazole acyl thiourea derivatives were designed based on a previously obtained pyrazolamide acyl lead compound, employing a scaffold hopping strategy. The compounds were synthesized, their structures were characterized, and they were evaluated for herbicidal activities. The results indicate that exhibited exceptional herbicidal activity against and at a dosage of 90 g ai/ha, using the foliar spray method in a greenhouse. This performance is comparable to that of commercial products, such as nicosulfuron and mesotrione. Moreover, showed moderate growth inhibitory activity against the young root and stem of at 200 mg/L in the small cup method, similar to that of nicosulfuron and mesotrione. Subsequent mode-of-action verification experiments revealed that and inhibited TKL (TKL) enzyme activity, with IC values of 0.740 and 0.474 mg/L, respectively. Furthermore, they exhibited inhibitory effects on the acetohydroxyacid synthase enzyme activity. Molecular docking predicted potential interactions between these ( and ) and TKL. A greenhouse experiment demonstrated that exhibited favorable crop safety at 150 g ai/ha. Therefore, is a promising herbicidal candidate that is worthy of further development.