4-Hydroxyphenylpyruvate dioxygenase
(HPPD) is an important target
for the development of new herbicides. HPPD inhibitors can hinder
photosynthesis and induce weed death with bleaching symptoms. To explore
the novel skeleton of HPPD inhibitors, a series of novel pyrazole
amide derivatives were synthesized and evaluated for their inhibitory
effects on Arabidopsis thaliana HPPD
(AtHPPD) and herbicidal activities. Some compounds
had excellent inhibitory activities against AtHPPD.
Among them, compound B5 displayed top-rank inhibitory
activity against AtHPPD with an IC50 value
of 0.04 μM, which was obviously superior to that of topramezone
(IC50 value of 0.11 μM). Furthermore, compounds B2 and B7 had 100% herbicidal activities in Petri
dish assays against Portulaca oleracea and Amaranthus tricolor at 100 μg/mL.
In particular, compound B7 not only possessed strong AtHPPD inhibitory activity but also exhibited significant
preemergence herbicidal activity. However, compound B7 was completely harmless to soybean, cotton, and wheat. In addition,
the molecular docking and microscale thermophoresis measurement experiment
verified that compounds can bind well with AtHPPD via π–π interactions. The present work
provides a new approach for the rational design of more effective
HPPD inhibitors, and pyrazole amides could be used as useful substructures
for the development of new HPPD inhibitors and preemergence herbicidal
agents.