Research Progress on the Action Mechanism of Herbicide Safeners: A Review

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Tembotrione, a 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has been widely used in many types of plants. Tembotrione has been reported for its likelihood of causing injury and plant death to certain corn hybrids. Safeners are co-applied with herbicides to protect certain crops without compromising weed control efficacy. Alternatively, herbicide safeners may effectively improve herbicide selectivity. To address tembotrione-induced Zea mays injury, a series of novel ester-substituted cyclohexenone derivatives were designed using the fragment splicing method. In total, 35 title compounds were synthesized via acylation reactions. All the compounds were characterized using infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. The configuration of compound II-15 was confirmed using single-crystal X-ray diffraction. The bioactivity assay proved that tembotrione phytotoxicity to maize could be reduced by most title compounds. In particular, compound II-14 exhibited the highest activity against tembotrione. The molecular structure comparisons as well as absorption, distribution, metabolism, excretion, and toxicity predictions demonstrated that compound II-14 exhibited pharmacokinetic properties similar to those of the commercial safener isoxadifen-ethyl. The molecular docking model indicated that compound II-14 could prevent tembotrione from reaching or acting with Z. mays HPPD (PDB: 1SP8). Molecular dynamics simulations showed that compound II-14 maintained satisfactory stability with Z. mays HPPD. This research revealed that ester-substituted cyclohexenone derivatives can be developed as potential candidates for discovering novel herbicide safeners in the future.

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Bioactivity of Novel Ester-Substituted Cyclohexenone Derivatives as Safeners

Zhao

Wang

et al. 2023

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“…GST is crucially involved in the detoxification of herbicides at the plant growth stage and protects plants from oxidative damage. 41 To further explore the specific effects of compound V on GST activity, compounds V-12, V-14, V-24, and V-25 with better bioactivity were screened on the basis of the preliminary bioassay results. Moreover, the detoxification mechanism was further discussed, and the commercial safener isoxadifen-ethyl was used as a control (Table 3).…”

Section: -Cyclopentyl-3-(5-methylisoxazole-3-formyl)-5-methyl-13-oxaz...mentioning

confidence: 99%

Design, Synthesis, and Structure–Activity Relationship of Novel Aryl-Substituted Formyl Oxazolidine Derivatives as Herbicide Safeners

Kang

Shi

et al. 2023

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Nicosulfuron is the leading herbicide in the global sulfonylurea (SU) herbicide market; it was jointly developed by DuPont and Ishihara. Recently, the widespread use of nicosulfuron has led to increasingly prominent agricultural production hazards, such as environmental harm and influence on subsequent crops. The use of herbicide safeners can significantly alleviate herbicide injury to protect crop plants and expand the application scope of existing herbicides. A series of novel aryl-substituted formyl oxazolidine derivatives were designed using the active group combination method. Title compounds were synthesized using an efficient one-pot method and characterized by infrared (IR) spectrometry, 1H and 13C nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). The chemical structure of compound V-25 was further identified by X-ray single crystallography. The bioactivity assay and structure–activity relationship proved that nicosulfuron phytotoxicity to maize could be reduced by most title compounds. The glutathione S-transferase (GST) activity and acetolactate synthase (ALS) in vivo were determined, and compound V-12 showed inspiring activity comparable to that of the commercial safener isoxadifen-ethyl. The molecular docking model indicated that compound V-12 competed with nicosulfuron for the acetolactate synthase active site and that this is the protective mechanism of safeners. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions demonstrated that compound V-12 exhibited superior pharmacokinetic properties to the commercialized safener isoxadifen-ethyl. The target compound V-12 shows strong herbicide safener activity in maize; thus, it may be a potential candidate compound that can help further protect maize from herbicide damage.

“…Agricultural weeds remain a serious threat to crop production, and chemical herbicides are commonly used to control unwanted vegetation that grows within crops. − However, the long-term and excessive use of chemical herbicides often causes weed resistance, which ultimately results in a decline in their effectiveness. − Consequently, finding a highly active herbicide that can inhibit resistant weed biotypes remains a challenge for agrichemical developers. − To address this issue, the use of novel PPO-inhibiting herbicides has emerged as a promising strategy. , …”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Activity Evaluation of Benzoxazinone-Pyrimidinedione Hybrids as Potent Protoporphyrinogen IX Oxidase Inhibitor

Zheng,

Zuo,

Huang

et al. 2023

Protoporphyrinogen IX oxidase (PPO/Protox, E.C. 1.3.3.4) is recognized as one of the most important targets for herbicide discovery. In this study, we report our ongoing research efforts toward the discovery of novel PPO inhibitors. Specifically, we identified a highly potent new compound series containing a pyrimidinedione moiety and bearing a versatile building blockbenzoxazinone scaffold. Systematic bioassays resulted in the discovery of compound 7af, ethyl 4-( 7 [1,4]oxazin-4-yl)butanoate, which exhibited broad-spectrum and excellent herbicidal activity at the dosage of 37.5 g a.i./ha through postemergence application. The inhibition constant (K i ) value of 7af to Nicotiana tabacum PPO (NtPPO) was 14 nM, while to human PPO (hPPO), it was 44.8 μM, indicating a selective factor of 3200, making it the most selective PPO inhibitor to date. Moreover, molecular simulations further demonstrated the selectivity and the binding mechanism of 7af to NtPPO and hPPO. This study not only identifies a candidate that showed excellent in vivo bioactivity and high safety toward humans but also provides a paradigm for discovering PPO inhibitors with improved performance through molecular simulation and structure-guided optimization.