Design, Synthesis, and Herbicidal Activity of Coumarin-3-Acetamide Derivatives as Potential Transketolase Inhibitors

Abstract Transketolase (TKL; EC 2.2.1.1) has been confirmed to be a promising new herbicide target. In this study, two series of the coumarin-based compounds 12a–12j and 13a–13m were designed and synthesized based on TKL as the new target. Among them, compound 12c could significantly inhibit the activity of SvTKL (IC50: 0.96 μmol/L) in vitro. Notably, compound 12c exhibited inhibitory effects of over 90% against D. sanguinalis and A. retroflexus higher than those of the positive control (inhibition < 80%) at 375 g a.i./ ha via the pot spraying method. Additionally, compound 12c exhibited good safety (injury rate <10%) for wheat and maize at 375 g a.i./ha. Molecular docking and molecular dynamics simulation studies indicated that compound 12c has a strong binding ability and dynamic stability with SvTKL. Furthermore, ARG598 may contribute to the stabilization of 12c within the SvTKL active pocket. These findings establish coumarin-fusaric acid derivatives as promising leads for new herbicide development.