Discovery of Novel <i>N</i>-Isoxazolinylphenyltriazinones as Promising Protoporphyrinogen IX Oxidase Inhibitors

Wang, Dawei; Zhang, Ruibo; Yu, Shuyi; Liang, Lu; Ismail, Ismail; Li, Yonghong; Xu, Han; Wen, Xin; Xi, Zhen

doi:10.1021/acs.jafc.9b04844

Cited by 38 publications

(62 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A premix formulation of saflufenacil and trifludimoxazin was launched this year in Australia. This formulation is more effective in burndown application than other burndown herbicides and is a promising tool for the control of PPO-herbicidetolerant or -resistant weeds [46][47][48][49]. Nevertheless, to curtail further resistance evolution, it is crucial to use this new product with other herbicide modes of action.…”

Section: Resistance Level To Fomesafen and Overall Response To Other Foliar-applied Herbicidesmentioning

confidence: 99%

PPO2 Mutations in Amaranthus palmeri: Implications on Cross-Resistance

et al. 2021

View full text Add to dashboard Cite

In Arkansas, resistance to protoporphyrinogen IX oxidase (PPO)-inhibiting herbicides in Amaranthus palmeri S. Wats. is mainly due to target site mutations. Although A. palmeri PPO-mutations are well investigated, the cross-resistance that each ppo mutant endows to weed populations is not yet well understood. We aimed to evaluate the response of PPO-resistant A. palmeri accessions, harboring the ppo2 mutations ΔG210 and G399A, to multiple PPO-inhibiting herbicides. Six resistant and one susceptible field accessions were subjected to a dose–response assay with fomesafen, and selected survivors from different fomesafen doses were genotyped to characterize the mutation profile. The level of resistance to fomesafen was determined and a cross-resistance assay was conducted with 1 and 2 times the labeled doses of selected PPO herbicides. The accession with higher predicted dose to control 50% of the population (ED50) had a higher frequency of ΔG210-homozygous survivors. Survivors harboring both mutations, and those that were ΔG210-homozygous, incurred less injury at the highest fomesafen rate tested (1120 g ai ha−1). The populations with a high frequency of ΔG210-homozygous survivors, and those with individuals harboring ΔG210 + G399A mutations, exhibited high potential for cross-resistance to other PPO herbicides. The new PPO–herbicide chemistries (saflufenacil, trifludimoxazin) generally controlled the PPO-resistant populations.

show abstract

Section: Resistance Level To Fomesafen and Overall Response To Other Foliar-applied Herbicidesmentioning

confidence: 99%

PPO2 Mutations in Amaranthus palmeri: Implications on Cross-Resistance

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Compound 1 and diflufenican were used as positive controls. The tested methods were the same as our previous reports [17,[23][24][25][26]. Briefly, for the pre-emergence herbicidal activity assays, the tested compounds in solvent (containing Tween-80 + DMF) were sprayed on the surface of the soil in the cups.…”

Section: Herbicidal Activity Assaymentioning

confidence: 99%

“…The parameters for the molecular dynamic (MD) simulations were prepared using the tleap program, the optimization of the 2a-Synechococcus PDS complex was performed using Sander, and the production of MD was performed using the pmemd module. The set of detailed parameters, the binding free energy calculation, and energy decomposition were the same as in the previous reports [25,30,31].…”

Section: Mocelcuar Simulation Studiesmentioning

confidence: 99%

In Silico Structure-Guided Optimization and Molecular Simulation Studies of 3-Phenoxy-4-(3-trifluoromethylphenyl)pyridazines as Potent Phytoene Desaturase Inhibitors

Yang

Wang

et al. 2021

Molecules

Self Cite

View full text Add to dashboard Cite

A series of novel 3-phenoxy-4-(3-trifluoromethylphenyl)pyridazines 2–5 were designed, based on the structure of our previous lead compound 1 through the in silico structure-guided optimization approach. The results showed that some of these new compounds showed a good herbicidal activity at the rate of 750 g ai/ha by both pre- and post-emergence applications, especially compound 2a, which displayed a comparable pre-emergence herbicidal activity to diflufenican at 300–750 g ai/ha, and a higher post-emergence herbicidal activity than diflufenican at the rates of 300–750 g ai/ha. Additionally, 2a was safe to wheat by both pre- and post-emergence applications at 300 g ai/ha, showing the compound’s potential for weed control in wheat fields. Our molecular simulation studies revealed the important factors involved in the interaction between 2a and Synechococcus PDS. This work provided a lead compound for weed control in wheat fields.

show abstract

“…We recently reported a series of highly efficient N -isoxazolinylphenyltriazinone PPO inhibitors. Among them, compounds with a fluorine atom at the 2-position and a chlorine atom at the 4-position of the benzene ring were found to show superior herbicidal and PPO inhibition activities . Therefore, designing novel inhibitors based on the 2-fluoro-4-chloro-5-isoxazolinylphenyl motif may provide an effective strategy for discovering new herbicides.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Molecular Mechanism Studies of N-Phenylisoxazoline-thiadiazolo[3,4-a]pyridazine Hybrids as Protoporphyrinogen IX Oxidase Inhibitors

Zhang

Liang

et al. 2020

J. Agric. Food Chem.

Self Cite

View full text Add to dashboard Cite

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for green agrochemical discovery. Herein, a novel N-phenylisoxazoline-thiadiazolo[3,4-a]pyridazine herbicidal active scaffold was designed by the scaffold hybridization strategy. Systematic structural optimization enabled the discovery of a series of derivatives with excellent weed control at 9.375–150 g ai/ha by the post-emergent application. Some derivatives exhibited improved Nicotiana tabacum PPO (NtPPO)-inhibitory activity than fluthiacet-methyl. Of these, 2b, with K i = 21.8 nM, displayed higher weed control than fluthiacet-methyl at the rate of 12–75 g ai/ha, and selective to maize at 75 g ai/ha. In planta, 2b was converted into a bioactive metabolite 5 (K i = 4.6 nM), which exhibited 4.6-fold more potency than 2b in inhibiting the activity of NtPPO. Molecular dynamics simulation explained that 5 formed stronger π–π interaction with Phe392 than that of 2b. This work not only provides a promising lead compound for weed control in maize fields but is also helpful to understand the molecular mechanism and basis of the designed hybrids.

show abstract

Discovery of Novel N-Isoxazolinylphenyltriazinones as Promising Protoporphyrinogen IX Oxidase Inhibitors

Cited by 38 publications

References 38 publications

PPO2 Mutations in Amaranthus palmeri: Implications on Cross-Resistance

PPO2 Mutations in Amaranthus palmeri: Implications on Cross-Resistance

In Silico Structure-Guided Optimization and Molecular Simulation Studies of 3-Phenoxy-4-(3-trifluoromethylphenyl)pyridazines as Potent Phytoene Desaturase Inhibitors

Design, Synthesis, and Molecular Mechanism Studies of N-Phenylisoxazoline-thiadiazolo[3,4-a]pyridazine Hybrids as Protoporphyrinogen IX Oxidase Inhibitors

Contact Info

Product

Resources

About