Design, Synthesis, and Antifungal Activity of N-(alkoxy)-Diphenyl Ether Carboxamide Derivates as Novel Succinate Dehydrogenase Inhibitors

Molecules, Год журнала: 2023, Номер 29(1), С. 83 - 83

Опубликована: Дек. 22, 2023

Succinate dehydrogenase (SDH, EC 1.3.5.1) is one of the most promising targets for fungicide development and has attracted great attention worldwide. However, existing commercial fungicides targeting SDH have led to increasingly prominent problem pathogen resistance, so it necessary develop new fungicides. Herein, we used a structure-based molecular design strategy synthesize series novel SDHI containing an N-(alkoxy)diphenyl ether carboxamide skeleton. The mycelial growth inhibition experiment showed that compound M15 exhibited very good control effect against four plant pathogens, with rates more than 60% at dose 50 μg/mL. A structure–activity relationship study found N-O-benzyl-substituted derivatives better antifungal activity others, especially introduction halogen on benzyl. Furthermore, docking results suggested π–π interactions Trp35 hydrogen bonds Tyr33 Trp173 were crucial interaction sites when inhibitors bound SDH. Morphological observation mycelium revealed could inhibit mycelia. Moreover, in vivo vitro tests not only inhibited enzyme but also effectively protected rice from damage due R. solani infection, result close concentration 200 Thus, skeleton starting point discovery worthy further investigation.

Язык: Английский

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

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 20, 2024

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

Язык: Английский

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Application of Difluoromethyl Isosteres in the Design of Pesticide Active Molecules

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Сен. 21, 2024

Difluoromethyl (CF

Язык: Английский

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Development and Biological Evaluation of New Diphenyl Ether Formylhydrazide Compounds as Potent Inhibitors of Succinate Dehydrogenase

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(47), С. 26133 - 26141

Опубликована: Ноя. 14, 2024

Succinate dehydrogenase (SDH), also recognized as succinate ubiquinone oxidoreductase (SQR), is considered one of the most promising targets for fungicide development, garnering significant international interest. We have focused on development highly effective, broad-spectrum-targeted SDH inhibitors. Using an active scaffold combining strategy, we designed and synthesized a series novel diphenyl ether formylhydrazine derivatives, compounds demonstrated broad-spectrum antifungal activity. Notably, compound

Язык: Английский

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Design, synthesis, X‐ray crystal structure, and antifungal evaluation of new acetohydrazide derivatives containing a 4‐thioquinazoline moiety

Pest Management Science, Год журнала: 2024, Номер unknown

Опубликована: Дек. 4, 2024

Abstract BACKGROUND To find efficient agricultural fungicides, 29 new 4‐thioquinazoline‐containing acetohydrazide derivatives were prepared and tested for their fungicidal properties. RESULTS All of the target compounds characterized by 1 H 13 C nuclear magnetic resonance high‐resolution mass spectrometry techniques, molecular structure compound A2 was verified single‐crystal X‐ray diffraction measurement. The experimental results revealed that many from this series had impressive inhibition efficacies in vitro against fungi. For example, A25 identified as best agent Rhizoctonia solani with an EC 50 (half‐maximal effective concentration) value 0.66 μg mL −1 , superior to those commercial fungicides chlorothalonil, carbendazim boscalid. Additionally, displayed favorable protection curative activities vivo rice sheath blight caused R . Antifungal mechanistic studies on indicated exerted its strong anti ‐R effects probably through fungal succinate dehydrogenase activity [half‐maximal inhibitory concentration (IC ) = 4.88 μ m ] impairment cell membrane integrity, based enzymatic bioassays, docking studies, scanning transmission electron microscopy observations. CONCLUSION Acetohydrazide containing 4‐thioquinazoline moiety potential be employed lead developing more near future. © 2024 Society Chemical Industry.

Язык: Английский

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