A systematic evaluation of zoxamide at enantiomeric level

Pan, Xinglu; Wu, Xiaomao; Liu, Na; Xu, Jun; Liu, Xingang; Wu, Xiaohu; Feng, Yueliang; Li, Runan; Dong, Fengshou; Zheng, Yongquan

doi:10.1016/j.scitotenv.2020.139069

Cited by 22 publications

(7 citation statements)

References 37 publications

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“…When the diameter of the colonies in the control group reached 7 cm, all of the diameters of the colonies were measured by using the cross method. The growth inhibition rate of the fenpropidin enantiomers to the pathogen was calculated on the basis of previous studies . The active contribution value of the efficient enantiomer was estimated according to formula .…”

Section: Methodsmentioning

confidence: 99%

Screening for a Fenpropidin Enantiomer with High Activity and Low Toxicity

Li,

Zhao,

Zhou

et al. 2023

J. Agric. Food Chem.

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Fenpropidin has been extensively used for managing fungal diseases in different crops. There is a lack of literature on the enantioselective bioactivity and toxicity of fenpropidin. This study aims to explore the enantioselective bioactivity and toxicity of fenpropidin. R-Fenpropidin exhibited more potent bioactivity against seven plant pathogens than S-fenpropidin. R-Fenpropidin was more effective than S-fenpropidin in inhibiting sclerotial production, affecting mycelial growth and morphology, increasing cell membrane permeability, and decreasing the ergosterol content of Rhizoctonia solani. R-Fenpropidin exhibited a tighter binding affinity and formed hydrogen bonds with two target proteins. Fenpropidin also has enantioselective toxicity to Selenastrum capricornutum, with the toxicity of S-fenpropidin being seven times that of R-fenpropidin. S-Fenpropidin significantly reduced the content of the photosynthetic pigments. The results showed that R-fenpropidin was a highly active enantiomer with low toxicity. This study can provide a basis for the development of enantiomers with high activity and low toxicity.

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Section: Methodsmentioning

confidence: 99%

Screening for a Fenpropidin Enantiomer with High Activity and Low Toxicity

Li,

Zhao,

Zhou

et al. 2023

J. Agric. Food Chem.

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“…20 This fungicide is commonly used as a racemic mixture, but a recent study reported that ZOX Renantiomer [(R)-ZOX] is 140-times more active against B. cinerea and less propense to degradation under aerobic conditions than the S-enantiomer [(S)-ZOX]. 21 RH-4032 (R,S enantiomeric mixture) is a ZOX analog that also exhibits tubulin polymerization inhibitory activity against plant cells (see Figure S1 of the Supporting Information). 16 Unlike DEF, BenS strain of B. cinerea is ZOX-sensitive, and a higher sensitivity to this benzamide has been reported for both BenR1 and BenR3 isolates.…”

Section: Introductionmentioning

confidence: 99%

“…Although several microtubule polymerization inhibitors have been cocrystallized within the tubulin, the ZOX binding site remains unknown to this day . Since all residues with reported mutations constitute the benzimidazole binding site in the β-tubulin, previous computational works have proposed different binding modes of ZOX at this pocket. ,, Nevertheless, none of these studies addressed the covalent binding of ZOX with the C239 residue. Herein, we employed a covalent molecular docking protocol to determine the most reliable binding pose of ZOX at the benzimidazole binding site.…”

Section: Introductionmentioning

confidence: 99%

Molecular Insights into the Covalent Binding of Zoxamide to the β-Tubulin of Botrytis cinerea

Velasco-Saavedra,

Mar-Antonio,

Aguayo-Ortiz

2023

J. Chem. Inf. Model.

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Botrytis cinerea is a fungal plant pathogen that causes significant economic losses in the agricultural industry worldwide. Fungicides that target microtubules, such as carbendazim (CBZ), diethofencarb (DEF), and zoxamide (ZOX), are widely used in crop protection against this pathogen. These groups of compounds exert their fungicidal activity by disrupting the microtubule assembly by binding to the β-tubulin subunit, provoking cellcycle arrest and cell death. However, with the appearance of isolates resistant to these compounds, it is necessary to search for new alternatives to control this pathogenic fungus. In this work, we gained insight into the binding and stability of these fungicides in the benzimidazole binding site of B. cinerea β-tubulin through different computational approaches. Our molecular dynamics simulation replicas showed that R enantiomers of ZOX and its analog RH-4032 had better interaction profiles at the site compared to S enantiomers. The simulations also revealed that while the R-isomer fungicides formed H-bonds with the main chain carbonyl of V236 or the side chain residue of S314, only CBZ interacted with E198. Previous experimental data have identified key mutations in B. cinerea's β-tubulin gene that lead to the development of resistance or, on the contrary, increased sensitivity for treatment with these fungicide compounds. In agreement with experimental findings, alchemical free energy calculations showed that E198A and E198V mutations in B. cinerea β-tubulin have high sensitivity to (R)-ZOX, whereas the E198K mutation decreased its affinity. Similarly, the results obtained explain the resistance to CBZ of B. cinerea isolates with E198A/V/K mutations and the insensitivity of the wild-type organism to DEF. Our work provides a deeper insight into the molecular mechanism of action of these fungicides, highlighting the importance of understanding the interaction profiles to develop more effective antifungal agents.

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“…Therefore, the development of the R-enantiomer in place of the racemate is a promising strategy to decrease usage without the loss of effectiveness against plant pathogens. 4 In the last decade, novel succinate dehydrogenase inhibitor (SDHI) fungicides have quickly evolved. 5 Penthiopyrad (PEN) is a novel SDHI chiral fungicide with high efficiency and broad-spectrum biological activity.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, the activity of R-zoxamide against plant pathogens was much higher than the S-enantiomer and racemate, and the nontarget toxicity of the R-enantiomer was 1.1–1.5 times higher than the racemate to Selenastrum capricornutum and Daphnia magna. Therefore, the development of the R-enantiomer in place of the racemate is a promising strategy to decrease usage without the loss of effectiveness against plant pathogens …”

Section: Introductionmentioning

confidence: 99%

Combined Analysis of Transcriptome and Metabolome Reveals the Potential Mechanism of the Enantioselective Effect of Chiral Penthiopyrad on Tomato Fruit Flavor Quality

Deng

Liu

et al. 2022

J. Agric. Food Chem.

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This study investigated the enantioselective effects of S-, R-, and rac-penthiopyrad (PEN) on the flavor quality of tomato fruit through the levels of sugars, acids, volatiles, and nutrients and explored the potential mechanism by combined analysis of the transcriptome and metabolome. The results revealed that the S-enantiomer increased the content of soluble sugars while decreasing the content of organic acids, thereby increasing the taste of tomato fruit. Furthermore, S-(+)-PEN promoted the accumulation of volatile compounds and nutrients (total phenols, flavonoids, and vitamin C). Transcriptome and metabolome data showed that the S-enantiomer improved fruit flavor and quality by influencing metabolites and genes in glycolysis, starch and sucrose metabolism, the citrate cycle, and amino acid biosynthesis pathways. However, R-(−)-PEN had a negative effect on tomato flavor. The effect of the racemate on fruit flavor quality was between a pair of enantiomers. The comprehensive data of PEN enantiomers will provide theoretical support for the application of PEN in tomatoes. Thus, developing enantiopure S-(+)-PEN products might be more conducive to the flavor and quality of the tomato fruit.

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A systematic evaluation of zoxamide at enantiomeric level

Cited by 22 publications

References 37 publications

Screening for a Fenpropidin Enantiomer with High Activity and Low Toxicity

Screening for a Fenpropidin Enantiomer with High Activity and Low Toxicity

Molecular Insights into the Covalent Binding of Zoxamide to the β-Tubulin of Botrytis cinerea

Combined Analysis of Transcriptome and Metabolome Reveals the Potential Mechanism of the Enantioselective Effect of Chiral Penthiopyrad on Tomato Fruit Flavor Quality

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