Synthesis of Novel Propionamide-Methylpyrazole Carboxylates as Herbicidal Candidates.

Transketolase (TKL; EC 2.2.1.1) is a highly promising potential target for herbicidal applications. To identify novel TKL inhibitors, we designed and synthesized a series of 3-oxopropionamide-1-methylpyrazole carboxylate analogues and assessed their herbicidal activities. Ethyl 3-((1-((2,4-dichlorophenyl)amino)-1-oxopropan-2-yl)oxy)-1-methyl-1-pyrazole-5-carboxylate () and ethyl 1-methyl-3-((1-oxo-1-((thiophen-2-ylmethyl)amino)propan-2-yl)oxy)-1-pyrazole-5-carboxylate () exhibited superior growth inhibition activities against both the root and stem of () compared to nicosulfuron and mesotrione. Additionally, achieved an inhibition rate of more than 90% against the roots and stems of (), outperforming the four control agents at a concentration of 200 mg/L using the small cup method. In the pre-emergence herbicidal activity test, effectively inhibited by more than 90% at 150 g ai/ha, surpassing the efficacy of the control, mesotrione. Conversely, in the postemergence herbicidal activity test, exhibited efficient inhibition of by more than 90% at 150 g ai/ha, outperforming the control agents nicosulfuron, mesotrione, and metamifop. The results of the TKL enzyme activity test showed that the IC values of compounds and were 0.384 and 0.655 mg/L, respectively, which were close to those of the control agents. Furthermore, molecular docking and molecular dynamics simulation studies revealed that and interacted favorably with the TKL of . Such findings highlight the promising potential of and as lead TKL inhibitors for the optimization of new herbicides.