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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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, Journal Year: 2023, Volume and Issue: 71(24), P. 9255 - 9265

Published: June 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.

Language: Английский

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Design and Synthesis of Novel Diphenyl Ether Carboxamide Derivatives To Control the Phytopathogenic Fungus Sclerotinia sclerotiorum

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(6), P. 2935 - 2942

Published: Feb. 5, 2024

Sclerotinia stem rot (SSR) caused by the phytopathogenic fungus sclerotiorum has led to serious losses in yields of oilseed rape and other crops every year. Here, we designed synthesized a series carboxamide derivatives containing diphenyl ether skeleton adopting scaffold splicing strategy. From results mycelium growth inhibition experiment, rates compounds 4j 4i showed more than 80% control S. at dose 50 μg/mL, which is close that positive (flubeneteram, 95%). Then, structure–activity relationship study benzyl was very important for antifungal activity introducing halogen atom on ring would improve activity. Furthermore, an vitro test suggested these novel can inhibit succinate dehydrogenase (SDH), binding mode with SDH basically similar flutolanil derivative. Morphological observation revealed compound could cause damage mycelial morphology cell structure sclerotiorum, resulting mycelia. vivo assessment displayed good (>97%) result concentration 200 mg/L. Thus, new starting point discovery inhibitors worthy further development.

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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Pyrazole derivatives: Recent advances in discovery and development of pesticides

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 110912 - 110912

Published: Feb. 1, 2025

Language: 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, Journal Year: 2022, Volume and Issue: 70(24), P. 7566 - 7575

Published: June 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.

Language: Английский

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Bioisosterism and Scaffold Hopping in Modern Nematicide Research

Journal of Agricultural and Food Chemistry, Journal Year: 2022, Volume and Issue: 70(36), P. 11042 - 11055

Published: May 12, 2022

The application of agrochemicals is critical to global food safety. Nowadays, environmentally friendly green are the trend in field crop protection. research and development nematicides absorbed more attention as a typical representation agrochemicals. This review describes origin recently commercialized nematicides, bioisosterism scaffold hopping discovery optimization agrochemicals, especially novel bioisosteric design strategies for identification fluensulfone analogues. Pesticide repurposing, high-throughput screening, computer-aided drug design, incorporation known pharmacophoric fragments have been most successful approach new nematicides. As outlined, replacements very approaches search sustainable In exploration analogues with nematicidal activity, replacement sulfone by amide, chain extension insertion methylene group, reversal amide group proven be yielded highly active These attempts might result compounds an optimal balance steric, hydrophobic, electronic, hydrogen-bonding properties contribute deal complex problem during Further ideas also put forward provide molecular

Language: Английский

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Exploration of Fungicidal Activity and Mode of Action of Ferimzone Analogs

Journal of Agricultural and Food Chemistry, Journal Year: 2023, Volume and Issue: 71(8), P. 3705 - 3718

Published: Feb. 10, 2023

Lead discovery and molecular target identification are important for developing novel pesticides. Scaffold hopping, an effective approach of modern medicinal agrochemical chemistry a rational design molecules, is aiming to molecules with similar structures similar/better biological performance. Herein, 24 new ferimzone derivatives were designed synthesized by scaffold-hopping strategy. In vitro bioassays indicated that compound 5o showed potency against Cercospora arachidicola 2-fold higher than Alternaria solani. Compounds 5q, 6a, 6d displayed fungicidal activity EC50 values ranging from 1.17 3.84 μg/mL Rhizoctonia solani, compounds 5q 6a 1.6–1.8-fold Fusarium graminearum. The in vivo at 200 was more potent Pyricularia oryzae (90% vs 70% efficacy, respectively). Density functional theory (DFT) calculations elucidated the structure–energy relationship. Although mode action still unclear, studies suggested significantly inhibited growth reproduction R. its energy metabolism pathways (e.g., starch, sucrose, lipids, glutathione) seriously downregulated after treatment.

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

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(12), P. 6691 - 6701

Published: March 18, 2024

To accelerate the development of novel fungicides, a variety

Language: Английский

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