Novel Pyrazole Acyl(thio)urea Derivatives Containing a Biphenyl Scaffold as Potential Succinate Dehydrogenase Inhibitors: Design, Synthesis, Fungicidal Activity, and SAR

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(5), С. 2512 - 2525

Опубликована: Янв. 29, 2024

As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, series new pyrazole acyl(thio)urea compounds containing diphenyl motif were designed and synthesized. Their structures confirmed by

Язык: Английский

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Design, Synthesis, Insecticidal Activity, and SAR of Aryl Isoxazoline Derivatives Containing Pyrazole-5-carboxamide Motif

Journal of Agricultural and Food Chemistry, Год журнала: 2023, Номер 71(40), С. 14458 - 14470

Опубликована: Окт. 2, 2023

It is important to develop new insecticides with a mode of action because increasing pesticide resistance. In this study, series novel aryl isoxazoline derivatives containing the pyrazole-5-carboxamide motif were designed and synthesized. Their structures confirmed by 1H NMR, 13C HRMS. Bioassays indicated that 24 compounds synthesized possessed excellent insecticidal activity against Mythimna separate no Aphis craccivora Tetranychus cinnabarinus. Among these derivatives, 3-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydrozol-3-yl)-N-(4-fluorophenyl)-1-methyl-1H-pyrazole-5-carboxamide (IA-8) had best M. separate, which comparable positive control fluralaner. The molecular docking results compound IA-8 fluralaner GABA model demonstrated same between in active site GABA. Molecular structure comparisons ADMET analysis can potentially be used design more compounds. structure–activity relationships are also discussed. This work provided an insecticide for further optimization.

Язык: Английский

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Discovery of Highly Efficient Novel Antifungal Lead Compounds Targeting Succinate Dehydrogenase: Pyrazole-4-carboxamide Derivatives with an N-Phenyl Substituted Amide Fragment

Journal of Agricultural and Food Chemistry, Год журнала: 2023, Номер 71(49), С. 19312 - 19323

Опубликована: Ноя. 29, 2023

Developing environmentally friendly fungicides is crucial to tackle the issue of rising pesticide resistance. In this study, a series novel pyrazole-4-carboxamide derivatives containing N-phenyl substituted amide fragments were designed and synthesized. The structures target compounds confirmed by 1H NMR, 13C HRMS, crystal structure most active compound N-(1-(4-(4-(tert-butyl)benzamido)phenyl)propan-2-yl)-3-(difluoromethyl)-N-methoxy-1-methyl-1H-pyrazole-4-carboxamide (U22) was further determined X-ray single-crystal diffraction. bioassay results indicated that 26 possessed good in vitro antifungal activity against Sclerotinia sclerotiorum with EC50 values for U12, U13, U15, U16, U18, U22, U23 being 4.17 ± 0.46, 8.04 0.71, 7.01 12.77 1.00, 8.11 0.70, 0.94 0.11, 9.48 0.83 μg·mL–1, respectively, which similar controls bixafen (6.70 0.47 μg·mL–1), fluxapyroxad (0.71 0.14 pydiflumetofen (0.06 0.01 μg·mL–1). Furthermore, vivo S. U12 (80.6%) U22 (89.9%) excellent preventative efficacy at 200 same as control (82.4%). Scanning electron microscopy transmission studies found could destroy hyphal morphology damage mitochondria, cell membranes, vacuoles. molecular docking succinate dehydrogenase (SDH) they interact well site SDH. This study validated our approach design strategy produce an enhanced biological compared parent structure.

Язык: Английский

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Targeting tubulin protein to combat fungal disease: Design, synthesis, and its new mechanistic insights of benzimidazole hydrazone derivatives

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 140226 - 140226

Опубликована: Янв. 1, 2025

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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Synthesis, crystal structure, Hirshfeld surface analysis, energy frameworks, molecular docking and DFT calculation of new pyrazole-4-carboxamide compound as antifungal agent

Journal of Molecular Structure, Год журнала: 2024, Номер 1317, С. 139145 - 139145

Опубликована: Июнь 30, 2024

Язык: Английский

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Synthesis and antimicrobial activity of functionally substituted 1,3-dioxacycloalkanes

Proceedings of universities Applied chemistry and biotechnology, Год журнала: 2025, Номер 14(4), С. 453 - 461

Опубликована: Янв. 12, 2025

One of the directions in development organic chemistry is synthesis biologically active compounds, including those with bactericidal activity, based on available petrochemical raw materials. In order to expand library bioactive compounds containing a 1,3-dioxacyclane fragment, derivatives 5-acyl-5-isopropyl-1,3-dioxane – 1-(5-isopropyl-1,3-dioxane-5-yl)ethanol and (5-isopropyl-1,3-dioxane-5-yl)ethyl phenyl carbamate was carried out. The effect synthesized fragment growth strains gram-negative gram-positive bacteria, lower fungi Candida albicans studied. It found that 2-methyl-2-ethyl-4-chloromethyl-1,3-dioxolane, chloromethyl group, has an antimicrobial against test cultures weak antifungal activity (minimum inhibitory concentration 100 μg/mL) albicans. 1-(5-Isopropyl-1,3-dioxan-5-yl)ethanol exhibits 2 sharply reduces Klebsiella pneumonia, Staphylococcus aureus, Enterobacter aerogenes μg/mL), contrast structurally similar 2-methyl-2-ethyl-4-hydroxymethyl-1,3-dioxolane, which did not show properties. 5-Acyl-5-isopropyl-1,3-dioxane, carbonyl group its structure, showed 25 cultures, exception Pseudomonas aeruginosa. Heterocycles (2-methyl-2-ethyl-4-chloromethyl-, 2-isobutyl-2,4-dimethyl-, 2-methyl-2-isobutyl-4-chloromethyl- 2-methyl-2-isobutyl-4-hydroxymethyl-1,3-dioxolane) at concentrations up μg/mL inhibit vital studied bacteria fungi. results obtained prospect continuing search for new drugs series 1,3-dioxacycloalkanes, structure fundamentally different from known antibacterial drugs.

Язык: Английский

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Addition of Diols to 2-Methylidene-1,4-dioxaspiro[4.5]decane

Russian Journal of Organic Chemistry, Год журнала: 2025, Номер 61(1), С. 190 - 193

Опубликована: Янв. 1, 2025

Язык: Английский

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Structural optimization of SDH‐targeting chalcone derivatives: piperazine‐driven binding stability against Xanthomonas pathogens

Pest Management Science, Год журнала: 2025, Номер unknown

Опубликована: Май 29, 2025

Abstract BACKGROUND Natural green pesticides have become a global research hotspot, and identifying chemical structural frameworks with excellent biological activity has the direction of numerous researchers. RESULTS Twenty chalcone derivatives incorporating 1,2,3,4‐tetrahydroquinoline scaffolds were systematically evaluated for their antibacterial against six plant pathogenic bacteria. Among tested compounds, H1–H10 exhibited superior in vitro inhibition Xanthomonas citri pv. mangiferaeindicae ( Xcm ) compared to Y1–Y10. Notably, compound H6 demonstrated exceptional potency, median effective concentration (EC 50 value 3.25 μg mL −1 , significantly surpassing commercial agent (TC, EC = 75.34 ). In vivo efficacy trials revealed that achieved 65.24% curative at 100 outperforming TC (42.81%). Scanning electron microscopy further confirmed H6's disruptive effects on bacterial membrane integrity. Mechanistic studies targeting succinate dehydrogenase (SDH), key respiratory enzyme, energetic similarities between SDH inhibitor bixafen through molecular docking dynamics simulations. CONCLUSION The moiety enhanced binding affinity, while introduced piperazine substructure improved both complex stability (root mean square deviation <1.5 Å) target engagement. These findings establish as promising lead developing next‐generation inhibitors, providing critical insights into structure–activity relationships agricultural antimicrobial design. © 2025 Society Chemical Industry.

Язык: Английский

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Synthesis, Antifungal Activity, and Molecular Simulation Study of L–Carvone‐Derived 1,3,4‐Oxadiazole‐Thioether Compounds

Chemistry & Biodiversity, Год журнала: 2023, Номер 20(7)

Опубликована: Июнь 29, 2023

Abstract To discover potent antifungal molecules with new and distinctive structures, 20 novel L‐carvone‐derived 1,3,4‐oxadiazole‐thioether compounds 5 a – t were synthesized through multi‐step reaction of L ‐ carvone, their structures confirmed by FT‐IR, 1 H‐NMR, 13 C‐NMR, HR‐MS. The activities preliminarily tested in vitro method, the results indicated that all title displayed certain against eight plant fungi, especially for P. piricola . Among them, compound i (R= p‐ F) most significant activity deserved further study discovering developing natural product‐based agents. Moreover, two molecular simulation technologies employed investigation structure–activity relationships (SARs). Firstly, reasonable effective 3D‐QSAR model was established comparative field (CoMFA) relationship substituents linked benzene rings inhibitory elucidated. Then, binding mode its potential biological target (CYP51) simulated docking, it found could readily bind CYP51 active site, ligand‐receptor interactions involved three hydrogen bonds several hydrophobic effects.

Язык: Английский

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