Identification of novel inhibitors of p-hydroxyphenylpyruvate dioxygenase using receptor-based virtual screening

Fu, Ying; Liu, Yongxuan; Kang, Tao; Sun, Yajuan; Li, Jiazhong; Ye, Fei

doi:10.1016/j.jtice.2019.08.005

Cited by 25 publications

(7 citation statements)

References 39 publications

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“…The best way to predict the interaction of small molecules with receptor binding pockets at the molecular level is molecular docking. − To understand the mechanism by which compound 6c and Oxyfluorfen acted on the target site of PPO, molecular docking experiments were carried out. As shown in Figure , the results showed that compound 6c and Oxyfluorfen had similar interactions with the surrounding amino acid residues but the interaction of compound 6c with amino acid residues was stronger than that of Oxyfluorfen.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Herbicidal Activity of Novel Diphenyl Ether Derivatives Containing Fast Degrading Tetrahydrophthalimide

Zhao

Jiang

et al. 2020

J. Agric. Food Chem.

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To seek new protoporphyrinogen oxidase (PPO) inhibitors with better biological activity, a series of novel diphenyl ether derivatives containing tetrahydrophthalimide were designed based on the principle of substructure splicing and bioisomerization. PPO inhibition experiments exhibited that 6c is the most potential compound, with the half-maximal inhibitory concentration (IC50) value of 0.00667 mg/L, showing 7 times higher activity than Oxyfluorfen (IC50 = 0.0426 mg/L) against maize PPO and similar herbicidal activities to Oxyfluorfen in weeding experiments in greenhouses and field weeding experiments. In view of the inspected bioactivities, the structure–activity relationship (SAR) of this series of compounds was also discussed. Crop selection experiments demonstrate that compound 6c is safe for soybeans, maize, rice, peanuts, and cotton at a dose of 300 g ai/ha. Accumulation analysis experiments showed that the accumulation of 6c in some crops (soybeans, peanuts, and cotton) was significantly lower than Oxyfluorfen. Current work suggests that compound 6c may be developed as a new herbicide candidate in fields.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Herbicidal Activity of Novel Diphenyl Ether Derivatives Containing Fast Degrading Tetrahydrophthalimide

Zhao

Jiang

et al. 2020

J. Agric. Food Chem.

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“…Protein–ligand crystal interactions were solvated through a simple point charge (SPC) water model with an orthogonal box with boundary conditions 46 . In addition, the OPLS_2005 force field was used to minimize the energy of the complex system at the maximum interaction of 2000 and a convergence threshold of 1.0 kcal mol Å −1 47 . The most rapid descent and limited‐memory Broyden–Fletcher–Goldfarb–Shanno (LBFGS) algorithm minimized the system energy in up to 5000 steps until a gradient threshold of 25 kcal mol Å −1 was reached.…”

Section: Methodsmentioning

confidence: 99%

Identification of 4‐hydroxyphenylpyruvate dioxygenase inhibitors by virtual screening, molecular docking, molecular dynamic simulation

et al. 2023

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BACKGROUND 4‐Hydroxyphenylpyruvate dioxygenase (HPPD) herbicides control broadleaf and gramineous weeds with better crop safety for corn, sorghum and wheat. Multiple screening models in silico have been established to obtain novel lead compounds as HPPD inhibition herbicides. RESULTS Topomer comparative molecular field analysis (CoMFA) combined with topomer search technology and Bayesian, genetic approximation functions (GFA) and multiple linear regression (MLR) models generated by calculating different descriptors were constructed for the quinazolindione derivatives of HPPD inhibitors. The coefficient of determination (r2) of topomer CoMFA, MLR and GFA were 0.975, 0.970 and 0.968, respectively; all the models established displayed excellent accuracy and high predictive capacity. Five compounds with potential HPPD inhibition were obtained via screening fragment library combined with the validation of the above models and molecular docking studies. After molecular dynamics (MD) validation and absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction, the compound 2‐(2‐amino‐4‐(4H‐1,2,4‐triazol‐4‐yl) benzoyl)‐3‐hydroxycyclohex‐2‐en‐1‐one not only exhibited stable interactions with the protein but also high solubility and low toxicity, and has potential as a novel HPPD inhibition herbicide. CONCLUSION In this study, five compounds were obtained through multiple quantitative structure–activity relationship screening. Molecular docking and MD experiments showed that the constructed approach had good screening ability for HPPD inhibitors. This work provided molecular structural information for developing novel, highly efficient and low‐toxicity HPPD inhibitors. © 2023 Society of Chemical Industry.

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“…Starting from the cocrystallyzed complex between AtHPPD and sulcotrione (entry 6isd of the protein data bank, Table 1), the receptor−ligand pharmacophore generation routine of the DiscoveryStudio software was applied to build a structurebased pharmacophoric model constituted by aromatic ring features that accounted for the interaction with Phe381 and Phe424, hydrophobic regions that contacted Pro280, and hydrogen bond acceptor/donor features that were responsible for iron chelation. 55 The model was then used to virtually screen the Zinc database and the prioritized compounds were further pruned by molecular docking and dynamics simulations. Six compounds were eventually identified (Figure 27), characterized by terminal phenyl and amide moieties linked by a four-or five-membered spacer.…”

Section: ■ Computer-driven Design and Identification Of Hppd Inhibitorsmentioning

confidence: 99%

Survey on the Recent Advances in 4-Hydroxyphenylpyruvate Dioxygenase (HPPD) Inhibition by Diketone and Triketone Derivatives and Congeneric Compounds: Structural Analysis of HPPD/Inhibitor Complexes and Structure–Activity Relationship Considerations

Governa

Bernardini

Braconi

et al. 2022

J. Agric. Food Chem.

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The serendipitous discovery of the HPPD inhibitors from allelopathic plants opened the way for searching new and effective herbicidal agents by application of classical hit-to-lead optimization approaches. A plethora of active and selective compounds were discovered that belong to three major classes of cyclohexane-based triketones, pyrazole-based diketones, and diketonitriles. In addition, to enhance inhibitory constant and herbicidal activity, many efforts were also made to gain broader weed control, crop safety, and eventual agricultural applicability. Moreover, HPPD inhibitors emerged as therapeutic agents for inherited and metabolic human diseases as well as vector-selective insecticides in the control of hematophagous arthropods. Given the large set of experimental data available, structure−activity relationship analysis could be used to derive suggestions for next generation optimized compounds.

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Identification of novel inhibitors of p-hydroxyphenylpyruvate dioxygenase using receptor-based virtual screening

Cited by 25 publications

References 39 publications

Design, Synthesis, and Herbicidal Activity of Novel Diphenyl Ether Derivatives Containing Fast Degrading Tetrahydrophthalimide

Design, Synthesis, and Herbicidal Activity of Novel Diphenyl Ether Derivatives Containing Fast Degrading Tetrahydrophthalimide

Identification of 4‐hydroxyphenylpyruvate dioxygenase inhibitors by virtual screening, molecular docking, molecular dynamic simulation

Survey on the Recent Advances in 4-Hydroxyphenylpyruvate Dioxygenase (HPPD) Inhibition by Diketone and Triketone Derivatives and Congeneric Compounds: Structural Analysis of HPPD/Inhibitor Complexes and Structure–Activity Relationship Considerations

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