<i>In vivo</i> fluorescent screening for <scp>HPPD‐targeted</scp> herbicide discovery

Fu, Yi‐Xuan; Zhang, Zi‐Ye; Guo, Wu‐Yingzheng; Dai, Yi‐Jie; Wang, Zheng‐Yu; Yang, Wen‐Chao; Yang, Guang‐Fu

doi:10.1002/ps.7117

Cited by 18 publications

(9 citation statements)

References 49 publications

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“…4-Hydroxyphenylpyruvate dioxygenase (HPPD) is a Fe(II)-dependent non-heme oxygenase that participates in the catabolic route of tyrosine and has different effects on plants, prokaryotes, and animals. − In plants, HPPD is critical for the biosynthesis of plastoquinone and tocopherol, which are crucial cofactors in photosynthesis. − Once HPPD is inhibited, the biosynthesis of plastoquinone and tocopherol is prevented. The conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid is blocked in plants, leading to a reduction in carotenoid production, obstruction of photosynthetic electron transport chain and chloroplast photooxidation, and onset of plant albino symptoms. , Currently, an important category of herbicides are pesticides with HPPD inhibitors . Three HPPD inhibitor herbicide families have been commercialized as herbicides and are broadly applied in agriculture, including the triketone family (tembotrione, mesotrione, and benzobicyclon), isoxazole family (isoxaflutole), and pyrazole family (topramezone) (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

“…7,8 Currently, an important category of herbicides are pesticides with HPPD inhibitors. 9 Three HPPD inhibitor herbicide families have been commercialized as herbicides and are broadly applied in agriculture, including the triketone family (tembotrione, mesotrione, and benzobicyclon), isoxazole family (isoxaflutole), and pyrazole family (topramezone) (Scheme 1). 10,11 HPPD-inhibiting herbicides are used to develop crops owing to their excellent herbicidal activity, broad-spectrum weed control capacity, outstanding crop selection, low mammalian toxicity, and superior environmental security.…”

Section: ■ Introductionmentioning

confidence: 99%

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

Zhao

Wang

et al. 2023

J. Agric. Food Chem.

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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.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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

Zhao

Wang

et al. 2023

J. Agric. Food Chem.

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“…A fluorescent platform for the targeted in vivo screening of 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors was proposed. The improved fluorescent label visualizes HPPD in living cells and in Danio fish for real-time direct monitoring of this enzyme inhibition [ 48 ].…”

Section: Current Trends In Herbicide Developmentmentioning

confidence: 99%

Modern Approaches for the Development of New Herbicides Based on Natural Compounds

Berestetskiy

2023

Plants

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Weeds are a permanent component of anthropogenic ecosystems. They require strict control to avoid the accumulation of their long-lasting seeds in the soil. With high crop infestation, many elements of crop production technologies (fertilization, productive varieties, growth stimulators, etc.) turn out to be practically meaningless due to high yield losses. Intensive use of chemical herbicides (CHs) has led to undesirable consequences: contamination of soil and wastewater, accumulation of their residues in the crop, and the emergence of CH-resistant populations of weeds. In this regard, the development of environmentally friendly CHs with new mechanisms of action is relevant. The natural phytotoxins of plant or microbial origin may be explored directly in herbicidal formulations (biorational CHs) or indirectly as scaffolds for nature-derived CHs. This review considers (1) the main current trends in the development of CHs that may be important for the enhancement of biorational herbicides; (2) the advances in the development and practical application of natural compounds for weed control; (3) the use of phytotoxins as prototypes of synthetic herbicides. Some modern approaches, such as computational methods of virtual screening and design of herbicidal molecules, development of modern formulations, and determination of molecular targets, are stressed as crucial to make the exploration of natural compounds more effective.

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“…However, these synthesized compounds did not exhibit satisfactory crop selectivity for the economic crops (peanut, soybean, and cotton), which is hard pressed to meet the abovementioned market demand. Therefore, we aimed to design novel HPPD inhibitors containing a triketone-quinazoline-2,4-dione skeleton through rational structural modifications, taking advantage of the developments in structural biology and chemical biology. − In pharmaceutical and agrochemical chemistry, the structure-based design strategy is recognized as an effective molecular design method for the discovery of candidate compounds, which is beneficial for efficiently improving the ligand binding affinity according to the known structure of the inhibitor–target complex. We previously reported the co-crystal structure of At HPPD– MBQ (Figure , PDB ID: 5YWK).…”

Section: Introductionmentioning

confidence: 99%

Structure-Based Design of 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor as a Potential Herbicide for Cotton Fields

Nan

Dong

Cao

et al. 2023

J. Agric. Food Chem.

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4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is one of the most promising herbicide targets for the development of agricultural chemicals owing to its unique mechanism of action in plants. We previously reported on the co-crystal structure of Arabidopsis thaliana (At) HPPD complexed with methylbenquitrione (MBQ), an inhibitor of HPPD that we previously discovered. Based on this crystal structure, and in an attempt to discover even more effective HPPD-inhibiting herbicides, we designed a family of triketone-quinazoline-2,4-dione derivatives featuring a phenylalkyl group through increasing the interaction between the substituent at the R1 position and the amino acid residues at the active site entrance of AtHPPD. Among the derivatives, 6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethyl-3-(1-phenylethyl)quinazoline-2,4(1H,3H)-dione (23) was identified as a promising compound. The co-crystal structure of compound 23 with AtHPPD revealed that hydrophobic interactions with Phe392 and Met335, and effective blocking of the conformational deflection of Gln293, as compared with that of the lead compound MBQ, afforded a molecular basis for structural modification. 3-(1-(3-Fluorophenyl)ethyl)-6-(2-hydroxy-6-oxocyclohex-1-ene-1-carbonyl)-1,5-dimethylquinazoline-2,4(1H,3H)-dione (31) was confirmed to be the best subnanomolar-range AtHPPD inhibitor (IC50 = 39 nM), making it approximately seven times more potent than MBQ. In addition, the greenhouse experiment showed favorable herbicidal potency for compound 23 with a broad spectrum and acceptable crop selectivity against cotton at the dosage of 30–120 g ai/ha. Thus, compound 23 possessed a promising prospect as a novel HPPD-inhibiting herbicide candidate for cotton fields.

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In vivo fluorescent screening for HPPD‐targeted herbicide discovery

Cited by 18 publications

References 49 publications

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

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

Modern Approaches for the Development of New Herbicides Based on Natural Compounds

Structure-Based Design of 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor as a Potential Herbicide for Cotton Fields

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