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, Journal Year: 2024, Volume and Issue: 72(5), P. 2512 - 2525

Published: Jan. 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

Language: 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, Journal Year: 2023, Volume and Issue: 71(40), P. 14458 - 14470

Published: Oct. 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.

Language: 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, Journal Year: 2023, Volume and Issue: 71(49), P. 19312 - 19323

Published: Nov. 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.

Language: 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, Journal Year: 2025, Volume and Issue: unknown, P. 140226 - 140226

Published: Jan. 1, 2025

Language: 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, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

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

Proceedings of universities Applied chemistry and biotechnology, Journal Year: 2025, Volume and Issue: 14(4), P. 453 - 461

Published: Jan. 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.

Language: Английский

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

Russian Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 61(1), P. 190 - 193

Published: Jan. 1, 2025

Language: 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, Journal Year: 2024, Volume and Issue: 1317, P. 139145 - 139145

Published: June 30, 2024

Language: Английский

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

Chemistry & Biodiversity, Journal Year: 2023, Volume and Issue: 20(7)

Published: June 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.

Language: Английский

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Synthesis, antifungal activity, and 3d-QSAR study of L- carvone-based pyrazole-oxime ester compounds

Natural Product Research, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 10

Published: Sept. 16, 2024

Natural products can provide versatile substructures with potential bioactivity and biocompatibility for exploring bioactive compounds. Herein, to explore novel natural product-derived antifungal agents, 21 unreported

Language: Английский

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