Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is one
of the most
important targets for the discovery of green herbicides. In order
to find novel PPO inhibitors with a higher herbicidal activity, a
series of novel N-phenyltriazinone derivatives containing
oxime ether and oxime ester groups were designed and synthesized based
on the strategy of pharmacophore and scaffold hopping. Bioassay results
revealed that some compounds showed herbicidal activities; especially,
compound B16 exhibited broad-spectrum and excellent 100%
herbicidal effects to Echinochloa crusgalli, Digitaria sanguinalis, Setaria faberii, Abutilon juncea, Amaranthus retroflexus, and Portulaca oleracea at a concentration of 37.5 g a.i./ha,
which were comparable to trifludimoxazin. Nicotiana
tabacum PPO (NtPPO) enzyme inhibitory
assay indicated that B16 showed an excellent enzyme inhibitory
activity with a value of 32.14 nM, which was similar to that of trifludimoxazin
(31.33 nM). Meanwhile, compound B16 revealed more safety
for crops (rice, maize, wheat, peanut, soybean, and cotton) than trifludimoxazin
at a dose of 150 g a.i./ha. Moreover, molecular docking and molecular
dynamics simulation further showed that B16 has a very
strong and stable binding to NtPPO. It indicated
that B16 can be used as a potential PPO inhibitor and
herbicide candidate for application in the field.