Novel fungicidal phenylethanol derivatives linking a trifluoromethyl pyrazole pharmacophore: design, synthesis, crystal structure, and biology evaluation

Tai, Lang; Sun, Shengxin; Yang, Kai; Chai, Jianqi; Hou, Shuaitao; Dai, Gui Yuan; Si, Weijie; Chen, Min

doi:10.1039/d3nj02234j

Cited by 5 publications

(2 citation statements)

References 45 publications

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“…The treatment with equal volume of the solvent DMSO (0.1 mL) was used as the blank control. The images were obtained using a SU8010 scanning electron microscope (Hitachi, Japan). − …”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors

Chai,

Wang,

Yue

et al. 2024

J. Agric. Food Chem.

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The dearomatization at the hydrophobic tail of the boscalid was carried out to construct a series of novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed and synthesized. Antifungal bioassays showed that the target compound E1 could selectively inhibit the in vitro growth of R. solani, with the EC50 value of 1.1 μg/mL that was superior to that of the agricultural fungicide boscalid (2.2 μg/mL). The observations by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) demonstrated that E1 could reduce mycelial density and significantly increase the mitochondrial number in mycelia cytoplasm, which was similar to the phenomenon treated with boscalid. Enzyme activity assay showed that the E1 had the significant inhibitory effect against the SDH from R. solani, with the IC50 value of 3.3 μM that was superior to that of boscalid (7.9 μM). The mode of action of the target compound E1 with SDH was further analyzed by molecular docking and molecular dynamics simulation studies. Among them, the number of hydrogen bonds was significantly more in the SDH-E1 complex than that in the SDH-boscalid complex. This research on the dearomatization strategy of the benzene ring for constructing pyrazole-4-carboxamides containing an oxime ether fragment provides a unique thought to design new antifungal drugs targeting SDH.

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“…The treatment with equal volume of the solvent DMSO (0.1 mL) was used as the blank control. The images were obtained using a SU8010 scanning electron microscope (Hitachi, Japan). − …”

Section: Methodsmentioning

confidence: 99%

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors

Chai,

Wang,

Yue

et al. 2024

J. Agric. Food Chem.

Self Cite

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“…The treatment with equal volume of the solvent DMSO (0.1 mL) was used as the blank control. The images were obtained using SU8010 scanning electron microscope (Hitachi, Japan) [61][62][63].…”

Section: Determination Of Sdh Inhibitory Activitymentioning

confidence: 99%

Design and optimization of novel succinate dehydrogenase inhibitors against agricultural fungi based on Transformer model

Zhang,

Chai,

et al. 2024

Preprint

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Succinate dehydrogenase inhibitors (SDHIs) are a promising class of fungicides targeting the energy production pathway of pathogenic fungi. However, overuse has led to resistance, necessitating the development of new and effective SDHIs. This study takes the Transformer model to generate a customized virtual library of potential SDHIs. These candidates were then meticulously screened based on expert knowledge and synthetic feasibility, ultimately yielding several pyrazole carboxamide derivatives as the promising leads. Subsequent synthesis, antifungal activity testing, and structural optimization further refined these leads into potent SDHI candidates. This work marks the first application of a generative model to SDHI design, establishing a robust workflow for virtual library generation, screening, activity evaluation, and structure optimization. This provides one way for the rational design of future SDHIs, not only against fungi, but potentially other agricultural pathogens as well.

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Novel quinazolin-4(3H)-one bionic-alkaloids bearing an 1,3,4-oxadiazole fragment as potential fungicides inhibiting Botrytis cinerea: Design, synthesis and bioactive-guided structural optimization

Wang,

Yan,

Zhang

et al. 2024

Arabian Journal of Chemistry

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Novel fungicidal phenylethanol derivatives linking a trifluoromethyl pyrazole pharmacophore: design, synthesis, crystal structure, and biology evaluation

Abstract: In order to find the compounds with novel structures and high antifungal activity, 26 phenylethanol derivatives containing a trifluoromethyl pyrazole pharmacophore were designed and synthesized by means of active group...

Cited by 5 publications

References 45 publications

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors

Design and optimization of novel succinate dehydrogenase inhibitors against agricultural fungi based on Transformer model

Novel quinazolin-4(3H)-one bionic-alkaloids bearing an 1,3,4-oxadiazole fragment as potential fungicides inhibiting Botrytis cinerea: Design, synthesis and bioactive-guided structural optimization

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