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 7a-7v were designed and synthesized through structural optimization for pyrazole-containing phenoxy amide compound 4u. Among the synthesized compounds, compound 7r possessed excellent herbicidal efficacy against Digitaria sanguinalis (Ds) and Amaranthus retroflexus (Ar) 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 7r 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 Setaria viridis (Sv)TKL and ligand, suggested that compound 7r acts as a typical TKL inhibitor, and the benzothiazole ring is an important motif for SvTKL inhibition activity. Above all, compound 7r could be a potential candidate for the development of herbicides with new MOA for weed control in maize and wheat field.

DFT calculation; herbicidal activity; herbicide target; molecular docking; pyrazole-carboxamides; transketolase.