Discovery of novel phenoxypyridine as promising protoporphyrinogen IX oxidase inhibitors

Zhao, Li‐Xia; Peng, Juan; Liu, Feng-yi; Zou, Yue-Li; Gao, Shuang; Fu, Ying; Ye, Fei

doi:10.1016/j.pestbp.2022.105102

Cited by 13 publications

(12 citation statements)

References 48 publications

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“…Protoporphyrinogen oxidase (PPO) [ 38 ] is a key enzyme in the biosynthesis of chlorophyll and heme in plants and is one of the important targets for the creation of novel herbicides. At present, PPO-inhibiting herbicides mainly include diphenyl ethers, phenylpyrazoles, triazolinones, N -phenyl phthalimides, and diazoles [ 39 ].…”

Section: Herbicides Containing Phenoxypyridine Scaffoldmentioning

confidence: 99%

Advancement of Phenoxypyridine as an Active Scaffold for Pesticides

Liu

Yong

et al. 2022

Molecules

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Phenoxypyridine, the bioisostere of diaryl ethers, has been widely introduced into bioactive molecules as an active scaffold, which has different properties from diaryl ethers. In this paper, the bioactivities, structure-activity relationships, and mechanism of compounds containing phenoxypyridine were summarized, which may help to explore the lead compounds and discover novel pesticides with potential bioactivities.

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Section: Herbicides Containing Phenoxypyridine Scaffoldmentioning

confidence: 99%

Advancement of Phenoxypyridine as an Active Scaffold for Pesticides

Liu

Yong

et al. 2022

Molecules

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“…Among them, chemical weeding still plays an important role in increasing crop yield. , For example, the use of herbicides with different modes of action can damage 90–99% of target weeds, which is also the most effective weed control method at present. However, the long-term use and abuse of herbicides will cause environmental pollution and pose potential risks to human health. − At the same time, weed species that are resistant to herbicide-active ingredients are also increasing year by year, which has become a problem that cannot be ignored. − Therefore, it is necessary to develop new environmentally friendly herbicides with high activity, low dose, broad spectrum, and low toxicity.…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Activity of Novel Phenyltriazolinone PPO Inhibitors Containing Five-Membered Heterocycles

Zhao,

Chen,

Luo

et al. 2024

J. Agric. Food Chem.

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Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX, which is a key step in the synthesis of porphyrins in vivo. PPO inhibitors use protoporphyrinogen oxidase as the target and block the biosynthesis process of porphyrin by inhibiting the activity of the enzyme, eventually leading to plant death. In this paper, phenyl triazolinone was used as the parent structure, and the five-membered heterocycle with good herbicidal activity was introduced by using the principle of substructure splicing. According to the principle of bioisosterism, the sulfur atoms on the thiophene ring were replaced with oxygen atoms. Finally, 33 phenyl triazolinones and their derivatives were designed and synthesized, and their characterizations and biological activities were investigated. The in vitro PPO inhibitory activity and greenhouse herbicidal activity of 33 target compounds were determined, and compound D4 with better activity was screened out. The crop safety determination, field weeding effect determination, weeding spectrum determination, and crop metabolism study were carried out. The results showed that compound D4 showed good safety to corn, soybean, wheat, and peanut but poor selectivity to cotton. The field weeding effect of this compound is comparable to that of the commercial herbicide sulfentrazone. The herbicidal spectrum experiment showed that compound D4 had a wide herbicidal spectrum and a good growth inhibition effect on dicotyledonous weeds. Molecular docking results showed that compound D4 forms a hydrogen bond with amino acid residue Arg-98 in the tobacco mitochondria (mtPPO)-active pocket and forms two π–π stacking interactions with Phe-392. This indicates that compound D4 has stronger PPO inhibitory activity. This indicates that compound D4 has wide prospects for development.

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“…It is the last isoenzyme in the synthesis of biological tetrahydropyrrole. It has been found in the inner mitochondrial membrane, chloroplast membrane, inner capsule, and protoplasm membrane. − When PPO is inhibited, protoporphyrinogen IX accumulates in large quantities and penetrates into the cytoplasm and is oxidized to produce a large amount of protoporphyrin IX. , Under the action of molecular oxygen, singlet oxygen is generated, resulting in the peroxidation and degradation of unsaturated fatty acids in the cell membrane, leading to plant cell death and ultimately plant death, which is manifested as leaf albino. , At present, the protoporphyrinogen oxidase inhibitor herbicides on the market are roughly divided into phenylpyrazole, triazolinone, diphenyl ether, oxadiazole, thiadiazole, pyrimidine dione, oxazolin dione, N -phenylphthalein imide, and others. − …”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, and Biological Activity Determination of Novel Phenylpyrazole Protoporphyrinogen Oxidase Inhibitor Herbicides Containing Five-Membered Heterocycles

Zhao,

Chen,

et al. 2023

J. Agric. Food Chem.

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Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitor herbicides have attracted widespread attention in recent years as ideal herbicides due to their high efficiency, low toxicity, and low pollution. In this article, 30 phenylpyrazole derivatives containing five-membered heterocycles were designed and synthesized according to the principle of bioelectronic isoarrangement and active substructure splicing. A series of structural characterizations were performed on the synthesized compounds. The herbicide activity in greenhouse was evaluated to determine their growth inhibition effect on weeds, their IC 50 value through in vitro PPO enzyme activity measurement was calculated, and target compounds 2i and 3j that have herbicide effects comparable to pyraflufen-ethyl were selected. Crop safety experiments have shown that when the spraying concentration is 300 g of ai/ha, gramineous crops such as wheat, corn, and rice are more tolerant to compound 2i, with wheat exhibiting high tolerance, which is equivalent to the crop safety of pyraflufen-ethyl. Compound 2i can be used as a candidate herbicide for wheat, corn, and paddy fields, and the results are consistent with the cumulative concentration experiment. Molecular docking results showed that compound 2i interacted with the amino acid residue ARG-98 by forming two hydrogen bonds and interacted with the amino acid residue PHE-392 by forming two π−π stacking interactions, indicating that compound 2i has more excellent herbicidal activity than pyraflufen-ethyl and is expected to become a potential lead compound of phenylpyrazole PPO inhibitor herbicides.

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Discovery of novel phenoxypyridine as promising protoporphyrinogen IX oxidase inhibitors

Cited by 13 publications

References 48 publications

Advancement of Phenoxypyridine as an Active Scaffold for Pesticides

Advancement of Phenoxypyridine as an Active Scaffold for Pesticides

Design, Synthesis, and Biological Activity of Novel Phenyltriazolinone PPO Inhibitors Containing Five-Membered Heterocycles

Design, Synthesis, and Biological Activity Determination of Novel Phenylpyrazole Protoporphyrinogen Oxidase Inhibitor Herbicides Containing Five-Membered Heterocycles

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