Design, synthesis, SAR and molecular docking of novel green niacin-triketone HPPD inhibitor

Fu, Ying; Zhang, Shuai-Qi; Liu, Yongxuan; Wang, Jingyi; Gao, Shuang; Zhao, Li‐Xia; Ye, Fei

doi:10.1016/j.indcrop.2019.05.070

Cited by 73 publications

(83 citation statements)

References 33 publications

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“…The structure of AtHPPD was taken from the PDB data bank. All molecular modeling studies were carried out as previously reported [10,19,[32][33][34]. The results show that two main interactions exist between I12 and the AtHPPD (Figure 4), as was observed for mesotrione; the 1,3-dicarbonyl unit is chelated to the iron ion, and the aromatic ring moiety formed π-π interactions with Phe403 and Phe360.…”

Section: Hppd Inhibitionmentioning

confidence: 74%

“…The docking study was conducted with the method reported previously [10,19,[32][33][34]. Crystal structures of Arabidopsis thaliana HPPD (PDB ID: 1TFZ) with the native ligand, named DAS869 were downloaded from the Protein Data Bank.…”

Section: Docking Studymentioning

confidence: 99%

“…AtHPPD was prepared and purified according to the reported methods in the literature [19,20,[35][36][37]. The inhibition constant (K i ) was obtained and shown in Table 1 and Table 2.…”

Section: Enzyme Inhibition Studymentioning

confidence: 99%

“…Arabidopsis thaliana HPPD (AtHPPD) and its inhibitors have been reported to interact in two ways: 1) through 1,3-dicarbonyl bidentate chelation with the active center metal, and 2) through favorable sandwich π-π stacking interactions between aromatic rings and the Phe360, Phe403 residues of the active site. Thus, 1,3-dicarbonyl and aromatic moieties are indispensable pharmacophores for potent HPPDinhibiting compounds that interact with surrounding residues in AtHPPD [16][17][18][19].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

Wang¹,

Huang²,

Shu³

et al. 2020

Beilstein J. Org. Chem.

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A series of aryloxyacetic acid derivatives were designed and synthesized as 4-hydoxyphenylpyruvate dioxygenase (HPPD) inhibitors. Preliminary bioassay results reveal that these derivatives are promising Arabidopsis thaliana HPPD (AtHPPD) inhibitors, in particular compounds I12 (K i = 0.011 µM) and I23 (K i = 0.012 µM), which exhibit similar activities to that of mesotrione, a commercial HPPD herbicide (K i = 0.013 µM). Furthermore, the newly synthesized compounds show significant greenhouse herbicidal activities against tested weeds at dosages of 150 g ai/ha. In particular, II4 exhibited high herbicidal activity for pre-emergence treatment that was slightly better than that of mesotrione. In addition, compound II4 was safe for weed control in maize fields at a rate of 150 g ai/ha, and was identified as the most potent candidate for a novel HPPD inhibitor herbicide. The compounds described herein may provide useful guidance for the design of new HPPD inhibiting herbicides and their modification.

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Section: Hppd Inhibitionmentioning

confidence: 74%

Section: Docking Studymentioning

confidence: 99%

“…AtHPPD was prepared and purified according to the reported methods in the literature [19,20,[35][36][37]. The inhibition constant (K i ) was obtained and shown in Table 1 and Table 2.…”

Section: Enzyme Inhibition Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

Wang¹,

Huang²,

Shu³

et al. 2020

Beilstein J. Org. Chem.

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show abstract

“…HPPD inhibitory activity was determined by using a coupled enzyme method. 47 Using the coupled enzyme reaction, the inhibitory activity of synthesized compounds A11 and A17 was evaluated using topramezone, mesotrione, pyrazoxyfen, isoxaflutole and benzobicyclon as the positive control. Assays were performed in 96-well plates at 30 ∘ C using a UV-visible plate reader to monitor the generation of maleylacetoacetate at 318 nm.…”

Section: Hppd Inhibition Determinationmentioning

confidence: 99%

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

Cai

et al. 2019

Pest Management Science

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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

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Multivariate image analysis applied to quantitative structure–activity relationships and docking studies of recent hydroxyphenylpyruvate deoxygenase inhibitors

et al. 2023

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Background Mesotrione is a triketone widely used as an inhibitor of the hydroxyphenylpyruvate deoxygenase (HPPD) enzyme. However, new agrochemicals should be developed continuously to tackle the problem of herbicide resistance. Two sets of mesotrione analogs have been synthesized recently and they have demonstrated successful phytotoxicity against weeds. In this study, these compounds were joined to form a single data set and the HPPD inhibition of this enlarged library of triketones was modeled using multivariate image analysis applied to quantitative structure–activity relationships (MIA‐QSAR). Docking studies were also carried out to validate the MIA‐QSAR findings and to aid the interpretation of ligand‐enzyme interactions responsible for the bioactivity (pIC50). Results The MIA‐QSAR models based on van der Waals radii (rvdW), electronegativity (ε), and the rvdW/ε ratio as molecular descriptors were both predictive to an acceptable degree (r2 ≥ 0.80, q2 ≥ 0.68 and r2pred ≥ 0.68). Subsequently, partial least squares (PLS) regression parameters were applied to predict the pIC50 values of newly proposed derivatives, yielding a few promising agrochemical candidates. The calculated log P for most of these derivatives was found to be higher than that of mesotrione and the library compounds, indicating that they should be less prone to leach out and contaminate groundwater. Conclusion Multivariate image analysis descriptors corroborated by docking studies were capable of modeling the herbicidal activities of 68 triketones reliably. Due to the substituent effects at the triketone framework, particularly of a nitro group in R3, promising analogs could be designed. The P9 proposal demonstrated higher calculated activity and log P than commercial mesotrione. © 2023 Society of Chemical Industry.

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Design, synthesis, SAR and molecular docking of novel green niacin-triketone HPPD inhibitor

Cited by 73 publications

References 33 publications

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

Synthesis and herbicidal activities of aryloxyacetic acid derivatives as HPPD inhibitors

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

Multivariate image analysis applied to quantitative structure–activity relationships and docking studies of recent hydroxyphenylpyruvate deoxygenase inhibitors

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