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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The research progress in and perspective of potential fungicides: Succinate dehydrogenase inhibitors

Bioorganic & Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 50, P. 116476 - 116476

Published: Oct. 20, 2021

Language: Английский

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Design, Synthesis, and Antifungal Activity of Novel Thiophene/Furan-1,3,4-Oxadiazole Carboxamides as Potent Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2021, Volume and Issue: 69(45), P. 13373 - 13385

Published: Nov. 4, 2021

Succinate dehydrogenase (SDH) is known as an ideal target for the investigations of fungicides. To develop novel SDH inhibitors, 30 thiophene/furan-1,3,4-oxadiazole carboxamide derivatives were designed and synthesized. In in vitro antifungal assay, a majority compounds demonstrated fair to potent activity against seven tested phytopathogenic fungi. Compounds 4b, 4g, 4h, 4i, 5j showed remarkable Sclerotinia sclerotiorum, affording EC50 values ranging from 0.1∼1.1 mg/L. particular, compound 4i displayed most S. sclerotiorum (EC50 = 0.140 ± 0.034 mg/L), which was superior that boscalid 0.645 0.023 mg/L). A further morphological investigation revealed abnormal mycelia damaged cell structures 4i-treated by scanning electron microscopy. Furthermore, vivo assay 4g effective suppressing rape rot at dosage 200 inhibition also presented significant inhibitory with IC50 1.01 0.21 4.53 0.19 μM, respectively, or equivalent (3.51 2.02 μM). Molecular docking molecular dynamics simulation could form strong interactions key residues SDH. These results indicated this class be promising scaffold discovery development inhibitors.

Language: Английский

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Fabrication of Versatile Pyrazole Hydrazide Derivatives Bearing a 1,3,4-Oxadiazole Core as Multipurpose Agricultural Chemicals against Plant Fungal, Oomycete, and Bacterial Diseases

Journal of Agricultural and Food Chemistry, Journal Year: 2021, Volume and Issue: 69(30), P. 8380 - 8393

Published: July 23, 2021

Developing multipurpose agricultural chemicals is appealing in crop protection, thus eventually realizing the reduction and efficient usage of pesticides. Herein, an array versatile pyrazole hydrazide derivatives bearing a 1,3,4-oxadiazole core were initially synthesized biologically evaluated antifungal, antioomycetes, antibacterial activities. In addition, ring was replaced by correlative pyrrole, thiazole, indole scaffolds to extend molecular diversity. The results showed that most these hybrid compounds empowered with multifunctional bioactivities, which are exemplified a1–a6, b1–b3, b7, b10, b13, b18. For antifungal activity, minimal EC50 values could afford 0.47 (a2), 1.05 0.65 (a1), 1.32 μg/mL (b3) against corresponding fungi Gibberella zeae (G. z.), Fusarium oxysporum, Botryosphaeria dothidea, Rhizoctonia solani. vivo pot experiments corn scab (caused G. z.) revealed compound a2 effective protective curative activities 90.2 86.3% at 200 μg/mL, comparable those fungicides boscalid fluopyram. Further docking study enzymatic activity analysis (IC50 = 3.21 μM, a2) indicated target promising succinate dehydrogenase inhibitors. Additionally, b2 a4 yielded superior anti-oomycete toward Phytophora infestins Xanthomonas oryzae pv. 2.92 8.43 respectively. trials rice bacterial blight provided control efficiency within 51.2–55.3% (a4) better than bismerthiazol. Given their characteristics, structures should be positively explored as chemicals.

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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Expanding the Chemical Space of Succinate Dehydrogenase Inhibitors via the Carbon–Silicon Switch Strategy

Journal of Agricultural and Food Chemistry, Journal Year: 2021, Volume and Issue: 69(13), P. 3965 - 3971

Published: March 29, 2021

The carbon–silicon switch strategy has become a key technique for structural optimization of drugs to widen the chemical space, increase drug activity against targeted proteins, and generate novel patentable lead compounds. Flubeneteram, targeting succinate dehydrogenase (SDH), is promising fungicide candidate recently developed in China. We describe synthesis SDH inhibitors with enhanced fungicidal enlarge space flubeneteram by employing C–Si strategy. Several thus formed flubeneteram-silyl derivatives exhibited improved porcine compared compound positive controls. Disease control experiments conducted greenhouse showed that trimethyl-silyl-substituted W2 comparable even higher activities benzovindiflupyr flubeneteram, respectively, low concentration 0.19 mg/L soybean rust control. Furthermore, encouragingly performed slightly better than azoxystrobin was less active at 100 field trials. computational results silyl-substituted phenyl moiety could form strong van der Waals (VDW) interactions SDH. Our indicate an effective method development inhibitors.

Language: Английский

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Synthesis and Biological Activity of Novel Pyrazol-5-yl-benzamide Derivatives as Potential Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2021, Volume and Issue: 69(20), P. 5746 - 5754

Published: May 14, 2021

To promote the discovery and development of new fungicides, a series novel pyrazol-5-yl-benzamide derivatives were designed, synthesized by hopping inversion amide groups pyrazole-4-carboxamides, evaluated for their antifungal activities. The bioassay data revealed that compound 5IIc exhibited an excellent in vitro activity against Sclerotinia sclerotiorum with EC50 value 0.20 mg/L, close to commercial fungicide Fluxapyroxad (EC50 = 0.12 mg/L) Boscalid 0.11 mg/L). For Valsa mali, 3.68 showed significantly higher than 12.67 14.83 In addition, vivo experiments proved has protective fungicidal inhibitory rate 97.1% S. at 50 while positive control 98.6% effect. molecular docking simulation interact TRP173, SER39, ARG43 succinate dehydrogenase (SDH) through hydrogen bond p−π interaction, which could explain probable mechanism action between target protein. Also, SDH enzymatic inhibition assay was carried out further validate its mode action. These results demonstrate be promising candidate provide valuable reference investigation.

Language: Английский

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Discovery of a Fungicide Candidate Targeting Succinate Dehydrogenase via Computational Substitution Optimization

Journal of Agricultural and Food Chemistry, Journal Year: 2021, Volume and Issue: 69(44), P. 13227 - 13234

Published: Oct. 28, 2021

Succinate dehydrogenase (SDH, EC 1.3.5.1) has proven to be an important fungicidal target, and the inhibition of SDH is useful in treatment plant pathogens. The discovery a novel active inhibitor high value. Herein, we disclose potent, highly as fungicide candidate by using computational substitution optimization method, fast drug design method developed our laboratory. greenhouse experiments showed that compound 17c exhibited protective activity against south corn rust, soybean rust (SBR), rice sheath blight at very low dosage 0.781 mg/L. Moreover, field trials indicated comparable even better than commercial fungicides SBR cucumber powdery mildew 50 mg/L concentration. Most surprisingly, resulted strictly curative benzovindiflupyr. computation results could form another hydrogen bond with C_S42 then lead strong van der Waals electronic interactions SDH. Our suggested potential for

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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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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