4-Hydroxyphenylpyruvate Dioxygenase Inhibitors: From Chemical Biology to Agrochemicals

Ndikuryayo, Ferdinand; Moosavi, Behrooz; Yang, Wen‐Chao; Yang, Guang‐Fu

doi:10.1021/acs.jafc.7b03851

Cited by 112 publications

(98 citation statements)

References 112 publications

(335 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Comparing the distances of the π–π stacking interactions, it can be seen that the distance between the benzene ring of intermediate 9 and Phe 360 is 4.6 Å, and Phe 403 is 4.0 Å; the distance between the benzene ring of DAS869 and Phe 360 is 4.5 Å, and Phe 403 is 4.5 Å. The results of molecular docking are consistent with those reported in the literature …”

Section: Resultssupporting

confidence: 90%

“…During the past 30 years, about 40 HPPD protein structures have been reported in PDBs . To further explore the interaction of the novel compound with HPPD at the molecular level, a docking study was carried out using Discovery Studio 2.5. In order to compare the binding mode of pyrazole HPPD inhibitor with HPPD, the reported crystal structure of At HPPD in complex with pyrazole HPPD inhibitor DAS869 (PDB code 1TFZ) was selected for docking simulation.…”

Section: Resultsmentioning

confidence: 99%

“…During the past 30 years, about 40 HPPD protein structures have been reported in PDBs . 57,58 To further explore the interaction of the novel compound with HPPD at the molecular level, a docking study was carried out using Discovery Studio 2.5. In order to wileyonlinelibrary.com/journal/ps…”

Section: Molecular Dockingmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor

Cai

et al. 2019

Pest Management Science

View full text Add to dashboard Cite

BACKGROUND 4‐Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been a good target for herbicide discovery. In order to discover novel HPPD herbicides, a series of pyrazole aromatic ketone analogs were designed and synthesized. RESULTS The 25 pyrazole aromatic ketone analogs synthesized were tested for herbicidal activity and compounds A1, A3, A4, A17, A20 and A25 displayed excellent herbicidal activity against Chenopodium serotinum, Stellaria media and Brassica juncea at 37.5 g ha−1. In addition, compounds A1, A5, A9, A10, A16, A17, A20 and A25 exhibited good crop selectivity for wheat, maize and rice at 150 g ha−1. Inhibition activities against AtHPPD proved the compounds were HPPD inhibitors. The structure–activity relationship of these pyrazole aromatic ketone analogs was studied using molecular docking. CONCLUSION These pyrazole aromatic ketone derivatives could be used as lead structures for development of HPPD herbicides against dicotyledonous weeds with further structure modification. © 2019 Society of Chemical Industry

show abstract

Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor

Cai

et al. 2019

Pest Management Science

View full text Add to dashboard Cite

show abstract

“…In animals, HPPD is required to modulate blood tyrosine levels, while in plants, it plays a key role in production of the aromatic precursor of tocopherols and plastoquinone. As plastoquinone is essential to photosynthetic organisms (Munné-Bosch and Alegre 2002; Norris et al 1995;Amesz 1973), HPPD is a target for the development of herbicides (Beaudegnies et al 2009;Ndikuryayo et al 2017). In Arabidopsis, the loss-of-function mutation of HPPD led to tocopherol and plastoquinone deficiency (Norris et al 1995(Norris et al , 1998.…”

Section: The General Tyrosine Metabolism Pathwaymentioning

confidence: 99%

General and specialized tyrosine metabolism pathways in plants

Fang

et al. 2019

aBIOTECH

View full text Add to dashboard Cite

The tyrosine metabolism pathway serves as a starting point for the production of a variety of structurally diverse natural compounds in plants, such as tocopherols, plastoquinone, ubiquinone, betalains, salidroside, benzylisoquinoline alkaloids, and so on. Among these, tyrosine-derived metabolites, tocopherols, plastoquinone, and ubiquinone are essential to plant survival. In addition, this pathway provides us essential micronutrients (e.g., vitamin E and ubiquinone) and medicine (e.g., morphine, salidroside, and salvianolic acid B). However, our knowledge of the plant tyrosine metabolism pathway remains rudimentary, and genes encoding the pathway enzymes have not been fully defined. In this review, we summarize and discuss recent advances in the tyrosine metabolism pathway, key enzymes, and important tyrosine-derived metabolites in plants.

show abstract

“…4‐Hydroxyphenylpyruvate dioxygenase (HPPD; http://www.chem.qmul.ac.uk/iubmb/enzyme/EC1/13/11/27.html), an Fe(II)‐dependent nonheme oxygenase, as a target, has shown great potential in drug discovery and crop protection due to its critical role in transforming 4‐hydroxyphenylpyruvate acid (HPPA) to homogentisate acid (HGA) in tyrosine metabolic pathway . In humans, abnormal tyrosine metabolism leads to diseases, including type I, type II, and type III tyrosinemia, hawkinsinuria, and alkaptonuria .…”

Section: Introductionmentioning

confidence: 99%

Molecular insights into the mechanism of 4‐hydroxyphenylpyruvate dioxygenase inhibition: enzyme kinetics, X‐ray crystallography and computational simulations

et al. 2019

View full text Add to dashboard Cite

Slow‐binding inhibitors with long residence time on the target often display superior efficacy in vivo. Rationally designing inhibitors with low off‐target rates is restricted by a limited understanding of the structural basis of slow‐binding inhibition kinetics in enzyme–drug interactions. 4‐Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for drug and herbicide development. Although the time‐dependent behavior of HPPD inhibitors has been studied for decades, its structural basis and mechanism remain unclear. Herein, we report a detailed experimental and computational study that explores structures for illustrating the slow‐binding inhibition kinetics of HPPD. We observed the conformational change of Phe428 at the C‐terminal α‐helix in the inhibitor‐bound structures and further identified that the inhibition kinetics of drugs are related to steric hindrance of Phe428. These detailed structural and mechanistic insights illustrate that steric hindrance is highly associated with the time‐dependent behavior of HPPD inhibitors. These findings may enable rational design of new potent HPPD‐targeted drugs or herbicides with longer target residence time and improved properties. Database Structure data are available in the PDB under the accession numbers (released), (released), and (released).

show abstract

4-Hydroxyphenylpyruvate Dioxygenase Inhibitors: From Chemical Biology to Agrochemicals

Cited by 112 publications

References 112 publications

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor

General and specialized tyrosine metabolism pathways in plants

Molecular insights into the mechanism of 4‐hydroxyphenylpyruvate dioxygenase inhibition: enzyme kinetics, X‐ray crystallography and computational simulations

Contact Info

Product

Resources

About