Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(4), P. 957 - 975

Published: Jan. 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.

Language: Английский

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Applications of Bioisosteres in the Design of Biologically Active Compounds

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(47), P. 18087 - 18122

Published: March 24, 2023

The design of bioisosteres represents a creative and productive approach to improve molecule, including by enhancing potency, addressing pharmacokinetic challenges, reducing off-target liabilities, productively modulating physicochemical properties. Bioisosterism is principle exploited in the bioactive compounds interest both medicinal agricultural chemists, this review, we provide synopsis applications where kind molecular editing has proved be advantageous molecule optimization. examples selected for discussion focus on carboxylic acids, fluorine fluorinated motifs compound design, some sulfoximine functionality, drug-H2O complexes, phenyl ring.

Language: 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, Journal Year: 2023, Volume and Issue: 71(4), P. 1862 - 1872

Published: Jan. 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.

Language: Английский

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Rational Exploration of Novel SDHI Fungicide through an Amide-β-ketonitrile Bioisosteric Replacement Strategy

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(14), P. 5483 - 5495

Published: March 28, 2023

The identification of succinate dehydrogenase inhibitor (SDHI) fungicides bearing a novel scaffold is great importance to control pathogenic fungi. Difluoromethyl-pyrazole β-ketonitrile derivatives were rationally designed through an innovative amide-β-ketonitrile bioisosteric replacement strategy and evaluated for their antifungal activities. In preliminary fungicidal screening, our new compounds showed outstanding in vitro activity. Compounds A7 A14 exhibited EC50 values 0.116 0.165 μg/mL against Sclerotinia sclerotiorum, respectively, also displayed 0.0774 Rhizoctonia solani. Furthermore, moderate vivo protective activity rice sheath blight on plants. Results from SDH enzymatic assays demonstrated that possesses significant inhibitory effect toward porcine heart SDH, with IC50 value 0.183 μM, which was 20-fold more potent than fluxapyroxad (IC50 = 3.76 μM). A docking study indicated H-bonds, cation−π interactions, edge-to-face π–π interactions play key roles the binding R. solani SDH. CoMSIA model guided approach further structural optimizations hydrophobic steric substituents benzene ring have decisive effects present work describes first time successful common SDHI amide moiety by group highlights potential β-ketonitriles as subclass.

Language: Английский

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An evolving view of complex II—noncanonical complexes, megacomplexes, respiration, signaling, and beyond

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(6), P. 104761 - 104761

Published: April 28, 2023

Mitochondrial complex II is traditionally studied for its participation in two key respiratory processes: the electron transport chain and Krebs cycle. There now a rich body of literature explaining how contributes to respiration. However, more recent research shows that not all pathologies associated with altered activity clearly correlate this role. Complex has been shown be necessary range biological processes peripherally related respiration, including metabolic control, inflammation, cell fate. Integration findings from multiple types studies suggests both participates respiration controls succinate-dependent signal transduction pathways. Thus, emerging view true function well beyond This review uses semichronological approach highlight major paradigm shifts occurred over time. Special emphasis given recently identified functions subunits because these have infused new directions into an established field.

Language: Английский

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Effects of single and combined exposure of virgin or aged polyethylene microplastics and penthiopyrad on zebrafish (Danio rerio)

The Science of The Total Environment, Journal Year: 2024, Volume and Issue: 921, P. 171160 - 171160

Published: Feb. 22, 2024

Language: Английский

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Functional Differentiation of the Succinate Dehydrogenase Subunit SdhC Governs the Sensitivity to SDHI Fungicides, ROS Homeostasis, and Pathogenicity in Fusarium asiaticum

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(18), P. 10314 - 10327

Published: April 25, 2024

Succinate dehydrogenase (SDH) is an integral component of the tricarboxylic acid cycle (TCA) and respiratory electron transport chain (ETC), targeted by succinate inhibitors (SDHIs). Fusarium asiaticum a prominent phytopathogen causing head blight (FHB) on wheat. Here, we characterized functions FaSdhA, FaSdhB, FaSdhC1, FaSdhC2, FaSdhD subunits. Deletion or resulted in significant growth defects F. asiaticum. The FaSdhC1 FaSdhC2 deletion mutants exhibited substantial reductions fungal growth, conidiation, virulence, reactive oxygen species (ROS). expression was significantly induced pydiflumetofen (PYD). ΔFaSdhC1 mutant displayed hypersensitivity to SDHIs, whereas ΔFaSdhC2 resistance against most SDHIs. transmembrane domains are essential for regulating mycelial sensitivity These findings provided valuable insights into how two SdhC paralogues regulated functional integrity SDH, ROS homeostasis, SDHIs phytopathogenic fungi.

Language: Английский

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Broad-spectrum chemicals block ROS detoxification to prevent plant fungal invasion

Current Biology, Journal Year: 2022, Volume and Issue: 32(18), P. 3886 - 3897.e6

Published: Aug. 5, 2022

Plant diseases cause a huge impact on food security and are of global concern. While application agrochemicals is common approach in the control plant currently, growing drug resistance off-target effects these compounds pose major challenges. The identification pathogenicity-related virulence mechanisms development new chemicals that target processes urgently needed. One such mechanism detoxification reactive oxygen species (ROS) generated by host plants upon attack pathogens. machinery ROS might therefore serve as for preventing diseases, but few anti-ROS-scavenging drugs have been developed. Here, we show model system Botrytis cinerea secretion cytochrome c-peroxidase, BcCcp1 removes plant-produced H2O2 promotes pathogen invasion. peroxidase modulated Tom1-like protein, BcTol1, through physical interaction. We BcTol1 regulated at different levels to enhance during early infection stage. Inactivation either or leads dramatically reduced B. cinerea. identify two BcTol1-targeting small molecules not only prevent invasion also effective activity against wide range fungal pathogens without detectable effect hosts. These findings reveal conserved fungi provide class potential fungicides diverse diseases. described here has implications further discovery related fields.

Language: Английский

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Design, Synthesis, Antifungal Activity, and Molecular Docking Studies of Novel Chiral Isoxazoline-Benzofuran-Sulfonamide Derivatives

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: April 15, 2024

Succinate dehydrogenase (SDH) is one of the most important molecular targets for development novel fungicides. With emerging problem resistance in plant fungal pathogens, compounds with high fungicidal activity need to be developed, but study chiral pesticides inhibition highly destructive pathogens has been rarely reported recent years. Therefore, a series isoxazoline-benzofuran-sulfonamide derivatives were designed investigate potential antifungal molecules. The target compound 3a was cultured as single crystal and confirmed using X-ray diffraction. All tested activity, 3c, 3i, 3s, 3r found have significant effects against S. sclerotiorum EC50 values 0.42 mg/L, 0.33 0.37 0.40 respectively, which superior commercial fungicide fluopyram (EC50 = 0.47 mg/L). IC50 value 3i SDH 0.63 mg/mL, further demonstrated by enzyme assays. Scanning electron microscopy showed that had inhibitory effect on sclerotiorum. In addition, fluorescence quenching analysis assay indicated similar positive control fluopyram. Molecular docking exhibited configuration better affinity than racemic configuration, possessed stronger action fluopyram, keeping vitro test results. These results would provide basis reference

Language: Английский

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Design, bioactivity and mechanism of N′-phenyl pyridylcarbohydrazides with broad-spectrum antifungal activity

Molecular Diversity, Journal Year: 2024, Volume and Issue: unknown

Published: June 26, 2024

Language: Английский

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