Design, Synthesis, and Herbicidal Activity Study of Novel Pyrazole-Carboxamides as Potential Transketolase Inhibitors.

Transketolase (TKL; EC 2.2.1.1) has been identified as a potential new herbicide target. In order to discover highly herbicidal active compounds targeting TKL and improve their structural diversity for lead compounds, a series of pyrazole-carboxamides - were designed and synthesized through structural optimization for pyrazole-containing phenoxy amide compound . Among the synthesized compounds, compound possessed excellent herbicidal efficacy against () and () by the small cup method (the inhibition about 95%, 100 mg/L) and the foliar spray method (the inhibition over 90%, 150 g ai/ha) in a greenhouse, which were superior to that of the positive control nicosulfuron. More significantly, compound displayed good crop selectivity toward both maize and wheat even at 375 g of ai/ha. The studies on mode of action (MOA) of high herbicidal active compounds, including the enzyme inhibition activity, fluorescent quenching experiments, and molecular docking analysis between ()TKL and ligand, suggested that compound acts as a typical TKL inhibitor, and the benzothiazole ring is an important motif for TKL inhibition activity. Above all, compound could be a potential candidate for the development of herbicides with new MOA for weed control in maize and wheat field.