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-1H-pyrazole-5-carboxylate (D15) and ethyl 1-methyl-3-((1-oxo-1-((thiophen-2-ylmethyl)amino)propan-2-yl)oxy)-1H-pyrazole-5-carboxylate (D20) exhibited superior
growth inhibition activities against both the root and stem of Amaranthus retroflexus (A. retroflexus) compared to nicosulfuron and mesotrione. Additionally, D15 achieved an inhibition rate of more than 90% against the roots and
stems of Digitaria sanguinalis (D. sanguinalis), outperforming the four control agents
at a concentration of 200 mg/L using the small cup method. In the
pre-emergence herbicidal activity test, D15 effectively
inhibited D. sanguinalis by more than
90% at 150 g ai/ha, surpassing the efficacy of the control, mesotrione.
Conversely, in the postemergence herbicidal activity test, D20 exhibited efficient inhibition of A. retroflexus 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 IC50 values of compounds D15 and D20 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 D15 and D20 interacted favorably with the TKL
of Setaria viridis. Such findings highlight
the promising potential of D15 and D20 as
lead TKL inhibitors for the optimization of new herbicides.