Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Год журнала: 2022, Номер 70(4), С. 957 - 975

Опубликована: Янв. 18, 2022

Up to now, a total of 24 succinate dehydrogenase inhibitors (SDHIs) fungicides have been commercialized, and SDHIs were also one the most active developed in recent years. Carboxamide derivatives represented an important class with broad spectrum antifungal activities. In this review, development carboxamide as great significances summarized. addition, structure–activity relationships (SARs) activities was summarized based on analysis structures commercial lead compounds. Moreover, cause resistance some solutions introduced. Finally, trend prospected. We hope review will give guide for novel future.

Язык: Английский

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Spectroscopic characterization (IR, UV-Vis), and HOMO-LUMO, MEP, NLO, NBO Analysis and the Antifungal Activity for 4-Bromo-N-(2-nitrophenyl) benzamide; Using DFT Modeling and In silico Molecular Docking

Journal of Molecular Structure, Год журнала: 2022, Номер 1271, С. 134001 - 134001

Опубликована: Авг. 26, 2022

Язык: Английский

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Potential Fungicide Candidates: A Dual Action Mode Study of Novel Pyrazole-4-carboxamides against Gibberella zeae

Journal of Agricultural and Food Chemistry, Год журнала: 2023, Номер 71(4), С. 1862 - 1872

Опубликована: Янв. 20, 2023

Pyrazole carboxamides are a class of traditional succinate dehydrogenase inhibitors (SDHIs) that have developed into variety commercialized fungicides. In the present work, series novel 1,5-disubstituted-1H-pyrazole-4-carboxamide derivatives were designed and synthesized based on active backbone 5-trifluoromethyl-1H-4-pyrazole carboxamide. Bioassay results indicated some target compounds exhibited excellent in vitro antifungal activities against six phytopathogenic fungi. Notably, EC50 values Y47 Gibberella zeae, Nigrospora oryzae, Thanatephorus cucumeris, Verticillium dahliae 5.2, 9.2, 12.8, 17.6 mg/L, respectively. The vivo protective curative at 100 mg/L G. zeae maize 50.7 44.2%, Three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis revealed large steric hindrance electronegative groups 5-position pyrazole ring important for activity. IC50 value (SDH) was 7.7 superior to fluopyram (24.7 mg/L), which consistent with docking results. Morphological studies fluorescence microscopy (FM) scanning electron (SEM) found could affect membrane integrity mycelium by inducing endogenous reactive oxygen species (ROS) production causing peroxidation cellular lipids, further verified malondialdehyde (MDA) content. Antifungal mechanism demonstrated compound not only had significant SDH inhibition activity but also mycelium, exhibiting obvious dual action modes. This research provides approach development SDHIs their derivatives.

Язык: Английский

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Design, Synthesis, and Antifungal Activities of Novel Pyrazole-4-carboxamide Derivatives Containing an Ether Group as Potential Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Год журнала: 2023, Номер 71(24), С. 9255 - 9265

Опубликована: Июнь 7, 2023

A series of novel pyrazole-4-carboxamides bearing an ether group were designed and synthesized on the basis structure commercial succinate dehydrogenase inhibitor (SDHI) fungicide flubeneteram via scaffold hopping evaluated for their antifungal activities against five fungi. The bioassay results showed that most target compounds exhibited excellent in vitro activity Rhizoctonia solani some exerted remarkable Sclerotinia sclerotiorum, Botrytis cinerea, Fusarium graminearum, Alternaria alternate. Particularly, 7d 12b displayed outstanding R. solani, with EC50 value 0.046 μg/mL, far superior to boscalid (EC50 = 0.741 μg/mL) fluxapyroxad 0.103 μg/mL). Meanwhile, compound also presented a broader fungicidal spectrum than other compounds. Moreover, vivo anti-R. could significantly inhibit growth rice leaves protective curative efficacies. In addition, (SDH) enzymatic inhibition assay generated significant SDH inhibition, IC50 3.293 μM, which was about 2 times better (IC50 7.507 μM) 5.991 μM). Furthermore, scanning electron microscopy (SEM) analysis indicated destroyed typical morphology hyphae. molecular docking study revealed embed into binding pocket form hydrogen bond interactions TRP173 TRY58 at site SDH, line fluxapyroxad, indicating they had similar mechanism action. These demonstrated be promising candidates SDHI fungicides, deserved further investigation.

Язык: Английский

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Discovery of N-Phenylpropiolamide as a Novel Succinate Dehydrogenase Inhibitor Scaffold with Broad-Spectrum Antifungal Activity on Phytopathogenic Fungi

Journal of Agricultural and Food Chemistry, Год журнала: 2023, Номер 71(8), С. 3681 - 3693

Опубликована: Фев. 15, 2023

Based on the structural features of both succinate dehydrogenase inhibitors (SDHIs) and targeted covalent inhibitors, a series N-phenylpropiolamides containing Michael acceptor moiety were designed to find new antifungal compounds. Nineteen compounds showed potent inhibition activity in vitro nine species plant pathogenic fungi. Compounds 9 13 higher most fungi than standard drug azoxystrobin. Compound could completely inhibit Physalospora piricola infection apples at 200 μg/mL concentration over 7 days high safety seed germination seedling growth plants ≤100 concentration. The action mechanism that is an SDH inhibitor with median inhibitory concentration, IC50, value 0.55 μg/mL, comparable positive boscalid. Molecular docking studies revealed can bind well ubiquinone-binding region by hydrogen bonds undergoes π–alkyl interaction π–cation interaction. At cellular level, 1 as parent compound destruct mycelial structure P. partly dissolve cell wall and/or membrane. Structure–activity relationship analysis acetenyl group should be determinant for activity, substitution pattern phenyl ring significantly impact activity. Thus, N-phenylpropiolamide emerged novel promising lead scaffold development SDHIs protection.

Язык: Английский

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Pyrazole derivatives: Recent advances in discovery and development of pesticides

Chinese Chemical Letters, Год журнала: 2025, Номер unknown, С. 110912 - 110912

Опубликована: Фев. 1, 2025

Язык: Английский

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Rational Design, Synthesis, and Biological Evaluation of Fluorine- and Chlorine-Substituted Pyrazol-5-yl-benzamide Derivatives as Potential Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Год журнала: 2022, Номер 70(24), С. 7566 - 7575

Опубликована: Июнь 8, 2022

To develop novel succinate dehydrogenase inhibitors (SDHIs), two series of N-4-fluoro-pyrazol-5-yl-benzamide and N-4-chloro-pyrazol-5-yl-benzamide derivatives were designed synthesized, their antifungal activities evaluated against Valsa mali, Sclerotinia sclerotiorum, FusaHum graminearum Sehw, Physalospora piricola, Botrytis cinerea. The bioassay results showed that some the target compounds exhibited good in vitro V. mali S. sclerotiorum. Remarkably, compound 9Ip displayed activity with an EC50 value 0.58 mg/L. This outcome was 21-fold greater than fluxapyroxad (12.45 mg/L) close to commercial fungicide tebuconazole (EC50 = 0.36 mg/L). In addition, vivo experiments proved has protective fungicidal inhibitory rate 93.2% at 50 mg/L, which equivalent positive control (95.5%). molecular docking indicated there obvious hydrogen bonds p-π interactions between (SDH), could explain probable action mechanism. SDH enzymatic inhibition assay carried out further prove its mode action. Our studies suggest be a lead discover more potent SDHIs for crop protection.

Язык: Английский

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Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(12), С. 6691 - 6701

Опубликована: Март 18, 2024

To accelerate the development of novel fungicides, a variety

Язык: Английский

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Recent Advances in Design and Development of Diazole and Diazine Based Fungicides (2014–2023)

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(28), С. 15427 - 15448

Опубликована: Июль 5, 2024

With fungal diseases posing a major threat to agricultural production, the application of fungicides control related is often considered necessary ensure world's food supply. The search for new bioactive agents has long been priority in crop protection due continuous development resistance against currently used types active compounds. Heterocyclic compounds are an inseparable part core structures numerous lead compounds, these rings constitute pharmacophores significant number developed over past decade by agrochemists. Among heterocycles, nitrogen-based play essential role. To date, diazole (imidazole and pyrazole) diazine (pyrimidine, pyridazine, pyrazine) derivatives make up important series synthetic fungicides. In recent years, many reports have published on design, synthesis, study fungicidal activity scaffolds, but there was lack comprehensive classified review nitrogen-containing scaffolds. Regarding this issue, here we reviewed articles families. current review, molecules synthesized so far based size ring.

Язык: Английский

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Discovery of Pyrazole-5-yl-amide Derivatives Containing Cinnamamide Structural Fragments as Potential Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Год журнала: 2023, Номер unknown

Опубликована: Ноя. 3, 2023

To promote the development of novel agricultural succinate dehydrogenase inhibitor (SDHI) fungicides, we introduced cinnamamide and nicotinamide structural fragments into structure pyrazol-5-yl-amide by carbon chain extension scaffold hopping, respectively, synthesized a series derivatives. The results biological activity assays indicated that most target compounds exhibited varying degrees inhibitory against tested fungi. Notably, G22, G28, G34, G38, G39 excellent in vitro antifungal activities Valsa mali with EC50 values 0.48, 0.86, 0.57, 0.73, 0.87 mg/L, this result was significantly more potent than boscalid (EC50 = 2.80 mg/L) closer to specialty control drug tebuconazole 0.30 mg/L). Compounds G22 G34 also vivo protective curative effects V. at 40 mg/L. SEM TEM observations may affect normal mycelial morphology as well cellular ultrastructure. Molecular docking analysis possessed similar binding mode SDH, detailed SDH inhibition validated feasibility designed potential inhibitors. G3 were selected for theoretical calculations, terminal carboxylic acid group be key region influencing activity. Furthermore, toxicity tests on Apis mellifera l. revealed low A. populations. above demonstrated these pyrazole-5-yl-amide derivatives are promising low-risk drug-resistance SDHI fungicides.

Язык: Английский

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