Design, synthesis and inhibitory activity of novel 2, 3-dihydroquinolin-4(1H)-one derivatives as potential succinate dehydrogenase inhibitors

Cheng, Wei; Yan, Yingkun; Xiao, Tingting; Zhang, Guilan; Zhang, Tingting; Lu, Tong; Jiang, Wenjing; Wang, Jingwen; Tang, Xiaorong

doi:10.1016/j.ejmech.2021.113246

Cited by 21 publications

(20 citation statements)

References 36 publications

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“…The key intermediates 3a−o were synthesized according to the previous literature. 8 The mixture of selected aldehyde (10.0 mmol), 3′,4′-(methylenedioxy)acetophenone (1, 10.0 mmol), and NaOH (20.0 mmol) in 20 mL anhydrous ethanol was stirred at room temperature for 3−4 h, and the reaction was monitored by TLC. After completion, the precipitate was filtered and washed with petroleum ether.…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…4−6 Since the first SDHI fungicide carboxin launched in 1966, 7 three generations of SDHIs have been developed and 24 of them have been applied as fungicidal pesticides. 8,9 The commercially used SDHIs, such as boscalid, 7 bixafen, 10 fluxapyroxad, 11 sedaxane, 12 and benzovindiflupyr, 13 have been utilized to protect various crops and products against a broad range of plant pathogenic fungi. However, due to the long-term use of several fungicidal agents, the resistance of plant pathogens to these pesticides has become a serious problem.…”

Section: ■ Introductionmentioning

confidence: 99%

“…In recent decades, succinate dehydrogenase (succinate-ubiquinone oxidoreductase or complex II) inhibitors (SDHI) have attracted wide attention and rapid development due to their specific targets and broad-spectrum fungicidal effects (Figure ). − Since the first SDHI fungicide carboxin launched in 1966, three generations of SDHIs have been developed and 24 of them have been applied as fungicidal pesticides. , The commercially used SDHIs, such as boscalid, bixafen, fluxapyroxad, sedaxane, and benzovindiflupyr, have been utilized to protect various crops and products against a broad range of plant pathogenic fungi. However, due to the long-term use of several fungicidal agents, the resistance of plant pathogens to these pesticides has become a serious problem.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and Fungicidal Evaluation of Novel 1,3-Benzodioxole-Pyrimidine Derivatives as Potential Succinate Dehydrogenase Inhibitors

Sun

Yang

Liu

et al. 2022

J. Agric. Food Chem.

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A series of novel 1,3-benzodioxole-pyrimidine derivatives were designed and synthesized. The in vitro bioassay indicated that compounds 4e, 4g, 4n, 5c, and 5e displayed excellent fungicidal activities against test fungal strains. Especially, in the in vitro experiments, 5c exhibited a broad spectrum of fungicidal activity against Botrytis cinerea, Rhizoctonia solani, Fusarium oxysporum, Alternaria solani, and Gibberella zeae with EC50 values of 0.44, 6.96, 6.99, 0.07, and 0.57 mg/L, respectively, which were significantly more potent than those of positive control boscalid (EC50: 5.02, >50, >50, 0.16, and 1.28 mg/L). In vivo testing on tomato fruits and leaves showed that 5c displayed considerable protective and curative efficacy against A. solani. Scanning electron microscopy analysis indicated that 5c possessed a strong ability to destroy the surface morphology of mycelia and seriously interfere with the growth of the fungal pathogen. In the in vitro enzyme inhibition assay, 5c exhibited pronounced succinate dehydrogenase (SDH) inhibitory activity with an IC50 value of 3.41 μM, equivalent to that of boscalid (IC50: 3.40 μM). In addition, fluorescence quenching experiment further confirmed the strong interaction of 5c with SDH. Through chiral resolution, 5c was separated into two enantiomers. Among them, (S)-5c exhibited stronger fungicidal activity (EC50: 0.06 mg/L) and SDH inhibitory (2.92 μM) activity than the R-enantiomer (EC50: 0.17 mg/L and SDH IC50: 3.68 μM), which was in accordance with the molecular docking study (CDOCKER Interaction Energy for (R)-5c and (S)-5c: −28.23 and −29.98 kcal/mol, respectively). These results presented a promising lead for the discovery of novel SDHIs as antifungal pesticides.

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Section: ■ Materials and Methodsmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, and Fungicidal Evaluation of Novel 1,3-Benzodioxole-Pyrimidine Derivatives as Potential Succinate Dehydrogenase Inhibitors

Sun

Yang

Liu

et al. 2022

J. Agric. Food Chem.

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“…In addition, compound 75 exhibited good inhibitory effect against SDH enzymes with IC 50 value of 0.251 mg/L, which was much better than that of fluopyram (IC 50 = 1.092 mg/L). 111 Compound 76 with a 4Hchromene group displayed excellent antifungal activity against S. sclerotiorum with EC 50 value of 0.063 μg/mL, which was about 4-fold more potent than that of fluopyram (EC 50 = 0.244 μg/mL). Furthermore, compound 76 exhibited strong inhibitory effect against SDH enzymes with IC 50 values of 0.095 μg/mL, far superior to fluopyram (IC 50 = 0.356 μg/ mL).…”

Section: Journal Ofmentioning

confidence: 96%

“…Among them, compound 75 containing 2,3-dihydroquinolin-4(1 H )-one skeletons showed promising antifungal activity against B. cinerea with EC 50 value of 0.132 mg/L, which was about 7-fold higher potency than that of the commercial fungicide fluopyram (EC 50 = 0.879 mg/L). In addition, compound 75 exhibited good inhibitory effect against SDH enzymes with IC 50 value of 0.251 mg/L, which was much better than that of fluopyram (IC 50 = 1.092 mg/L) . Compound 76 with a 4 H -chromene group displayed excellent antifungal activity against S. sclerotiorum with EC 50 value of 0.063 μg/mL, which was about 4-fold more potent than that of fluopyram (EC 50 = 0.244 μg/mL).…”

Section: Carboxamide Derivatives As Sdhismentioning

confidence: 97%

Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

Luo

Ning

2022

J. Agric. Food Chem.

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Up to now, a total of 24 succinate dehydrogenase inhibitors (SDHIs) fungicides have been commercialized, and SDHIs fungicides were also one of the most active fungicides developed in recent years. Carboxamide derivatives represented an important class of SDHIs with broad spectrum of antifungal activities. In this review, the development of carboxamide derivatives as SDHIs with great significances were summarized. In addition, the structure−activity relationships (SARs) of antifungal activities of carboxamide derivatives as SDHIs was also summarized based on the analysis of the structures of the commercial SDHIs and lead compounds. Moreover, the cause of resistance of SDHIs and some solutions were also introduced. Finally, the development trend of SDHIs fungicides was prospected. We hope this review will give a guide for the development of novel SDHIs fungicides in the future.

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Novel quinolin‐2(1H)‐one analogues as potential fungicides targeting succinate dehydrogenase: design, synthesis, inhibitory evaluation and molecular modeling

Wang

Xiao

et al. 2023

Pest Management Science

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BACKGROUNDSuccinate dehydrogenase is an important target of fungicides. Succinate dehydrogenase inhibitors (SDHIs) have widely been used to combat destructive plant pathogenic fungi because they possess efficient and broad‐spectrum antifungal activities and as well as unique mode of action. The research and development of novel SDHIs have been ongoing.RESULTSThirty‐six novel quinolin‐2(1H)‐one derivatives were designed, synthesized and characterized. The single crystal structure of compound 3c was determined through the X‐ray diffraction of single crystals. The bioassay results displayed that most compounds had good antifungal activities at 16 μg mL−1 against Rhizoctonia cerealis, Erysiphe graminis, Botrytis cinerea, Penicillium italicum and Phytophthora infestans. Compounds 6o, 6p and 6r had better antifungal activities than the commercialized fungicide pyraziflumid against Botrytis cinerea. Their half maximal effective concentration (EC50) values were 0.398, 0.513, 0.205 and 0.706 μg mL−1, respectively. Moreover, the inhibiting activities of the bioactive compounds were tested against succinate dehydrogenase. The results indicated that they possessed outstanding activities. Compounds 6o, 6p and 6r also exhibited better inhibiting activities than pyraziflumid against succinate dehydrogenase. Their half maximal inhibitory concentration (IC50) values were 0.450, 0.672, 0.232 and 0.858 μg mL−1, respectively. The results of molecular dynamic (MD) simulations indicated that compound 6r displayed stronger affinity to succinate dehydrogenase than pyraziflumid.CONCLUSIONThe results of the present study displayed that quinolin‐2(1H)‐one derivative could be one scaffold of potential SDHIs and will provide some valuable information for the research and development of new SDHIs. © 2022 Society of Chemical Industry.

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Design, synthesis and inhibitory activity of novel 2, 3-dihydroquinolin-4(1H)-one derivatives as potential succinate dehydrogenase inhibitors

Cited by 21 publications

References 36 publications

Design, Synthesis, and Fungicidal Evaluation of Novel 1,3-Benzodioxole-Pyrimidine Derivatives as Potential Succinate Dehydrogenase Inhibitors

Design, Synthesis, and Fungicidal Evaluation of Novel 1,3-Benzodioxole-Pyrimidine Derivatives as Potential Succinate Dehydrogenase Inhibitors

Comprehensive Overview of Carboxamide Derivatives as Succinate Dehydrogenase Inhibitors

Novel quinolin‐2(1H)‐one analogues as potential fungicides targeting succinate dehydrogenase: design, synthesis, inhibitory evaluation and molecular modeling

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