Design, Synthesis, and Fungicidal Evaluation of Novel Pyrazole-furan and Pyrazole-pyrrole Carboxamide as Succinate Dehydrogenase Inhibitors

Yao, Tingting; Xiao, Douxin; Li, Zhongshan; Cheng, Jing-Li; Fang, Shao‐Wei; Du, Yong-Jun; Zhao, Jinhao; Dong, Xiaowu; Zhu, Guonian

doi:10.1021/acs.jafc.7b01251

Cited by 55 publications

(30 citation statements)

References 26 publications

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“…Furthermore, the recent studies on the structural modification of amide SDHI fungicides mainly focused on the substituents in aromatic ring and polar moiety. [7][8][9][10][11][12][13][14] Recently, several literatures reported the effect of changes in the amide bridge on fungicidal activity, such as ⊍-hydroxy and ⊍-carbonyl chiral amide ( Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Studies on the novel pyridine sulfide containing SDH based heterocyclic amide fungicide

Hua

Liu

et al. 2020

Pest Management Science

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BACKGROUND: Succinate dehydrogenase (SDH) has been identified as one of the most significant targets for fungicide discovery. To date, 23 commercial SDH inhibitor (SDHI) fungicides have been approved for plant protection since the first launch of carboxin in 1966, and extensively applied to combat destructive plant fungi. RESULTS:In this project, 20 novel pyridine sulfide derivatives containing SDH-based heterocyclic amide fungicide were designed, synthesized, and characterized by proton nuclear magnetic resonance ( 1 H-NMR), carbon-13 ( 13 C)-NMR and highresolution mass spectrometry (HRMS). In vitro fungicidal activity experiment, the target compound I-1 displayed excellent inhibitory rates against the common agricultural pathogens with half maximal effective concentration (EC 50 ) values of 5.2 to 39.8 ∼g mL −1 . The in vivo fungicidal activities demonstrated that the compound I-1 could effectively prevent Botrytis cinerea from infecting tomato and cucumber leaves with the preventative rates of 67% and 50%. The mitochondrial membrane potential detection, SDH enzyme assay and the molecular docking simulation revealed that the mechanism of action of the compound I-1 and the relevant interactions with the target enzyme may be similar to those of the control fluopyram.CONCLUSION: The biological activity screening and validation of mechanism of action indicated that the compound I-1 could be identified as a potential SDH inhibitor for further study.

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Section: Introductionmentioning

confidence: 99%

Studies on the novel pyridine sulfide containing SDH based heterocyclic amide fungicide

Hua

Liu

et al. 2020

Pest Management Science

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“…In this work, a series of 37 compounds were used to generate the relationship between chemical traces of the compound and its antifungal activity. These 37 compounds of novel pyrazole-furan and pyrazolepyrrole carboxamide were obtained from the previous work [24]. The logarithm of the measured EC 50 (μM) against antifungal activity given by pEC 50 (p EC 50 = − log 1/EC 50 ) was taken as a dependent variable; therefore, the data was linearly correlated with the independent variables (descriptors) [10].…”

Section: Datasetmentioning

confidence: 99%

In silico studies of novel pyrazole-furan and pyrazole-pyrrole carboxamide as fungicides against Sclerotinia sclerotiorum

Isyaku

Uzairu

Shallangwa

2020

Beni-Suef Univ J Basic Appl Sci

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Background: Pyrazole-furan and pyrazole-pyrrole moiety are among the molecular structures that were found to have an extensive range of applications in the field of medicine and agrochemical due to their wide spectrum of biological activities. These include antimicrobial activity, anti-glaucoma activity, ocular hypertension activity, and antifungal activity. Results: An in silico study was carried out on 37 compounds of pyrazole-furan and pyrazole-pyrrole carboxamide derivatives against Sclerotinia sclerotiorum. Using Spartan 14 software, optimization of the compounds was performed at the DFT/B3LYP/6-31G* quantum mechanical method. PaDEL descriptor software was used to calculate the molecular descriptors, and a Generic Function Approximation (GFA) was employed to generate the model. Out of four models generated, model 1 was found to be the optimal and has the following statistical parameters; R 2 = 0.83485, R 2 adj = 0.793563, cross-validated R 2 = 0.74037, and external R 2 = 0.58479. Molecular docking study was carried out between the antifungal compounds, and the binding site of S. sclerotiorum (PDB CODE 2X2S) in which compound 7 was identified to have the highest binding energy of − 7.5kcal/mol. This compound "7" has a strong affinity with the macromolecular target point of the S. sclerotiorum (2x2s), producing H-bond and as well as the hydrophobic interaction at target point of the amino acid residue. Considering compound 7 as our scaffold, four (4) more potent compounds (7a, 7b, 7c, and 7d) were designed using optimization method of structure-based designed which have the following docking score, − 7.7, − 7.8, − 7.7, and − 7.7kcal/mol. Conclusion: Statistical analyses including variance inflation factor (VIF), mean effect (ME), and applicability domain were conducted on the model. Considering an interpretation of the descriptors given in the discussion, the QSAR model provided an idea of ligand-based design while the molecular docking gave an insight on structure-based design of the new compounds with better activity against S. sclerotiorum in which four (4) compounds 7a, 7b, 7c, and 7d were designed and discovered to be of high quality and have greater binding affinity compared to the one obtained from the literature (compound 7). BackgroundSclerotinia sclerotiorum otherwise called cottony rot, blossom blight, stem rot, crown rot, or watery soft rot, is a fungal pathogen that results in a plant disease known as "white mold" under favorable conditions. This pathogen produces black resting structures (called sclerotia) on the affected plant. It can be found in different parts of the world with an extensive range of hosts [4]. S. sclerotiorum causes great losses when onset on a favorable environmental and extensive care or control measures should drastically be taken [23]. Herbaceous, succulent plants (particularly flowers) and vegetables are the common hosts.Pyrazole-furan and pyrazole-pyrrole moiety are among the molecular structures found to have an extensive wide range of applications in the field of medic...

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“…There is therefore a need to discover new highly active compounds with high effectiveness, low toxicity and that are environmentally friendly, and which also may overcome resistance problems . Succinate dehydrogenase (SDH) is an ideal target for fungicidal agents . The first fungicidal agent carboxin targeting SDH was developed in the 1960s, and many succinate dehydrogenase inhibitor (SDHI) fungicides had been developed to protect fruit, vegetable and crops, for example, isopyrazam, furametpyr, fluxapyroxad, pydiflumetofen, penthiopyrad, bixafen, benzovindiflupyr and sedaxane (Fig.…”

Section: Introductionmentioning

confidence: 99%

Novel 4‐pyrazole carboxamide derivatives containing flexible chain motif: design, synthesis and antifungal activity

Liu

Zhai

et al. 2019

Pest Management Science

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Background In recent years, carboxamide fungicides, targeting succinate dehydrogenase (SDH), have shown highly efficient and broad spectrum fungicidal activity. Structure–activity relationship (SAR) results for these commercial fungicides show that the carboxamide group was a key active group. This is useful information for the discovery of new pyrazole carboxamide derivatives with fungicidal activity. Results Twenty‐seven novel pyrazole carboxamides were designed and synthesized. Their fungicidal activities against Gibberella zeae, Phytophthora infestans, Phytophthora capsici, Rhizoctonia solani, Alternaria solani, Botrytis cinerea, Fusarium oxysporum, Cercospora arachidicola, Sclerotinia sclerotiorum and Physalospora piricola were tested; derivatives possessed excellent inhibitory at 50 mg L−1 in particular. Furthermore, some pyrazole carboxamides exhibited remarkably high activities against Sclerotinia sclerotiorum in vitro with EC50 values of 2.04 to 15.2 μg mL−1. In addition, some compounds also exhibited high activities against Physalospora piricola, Cercospora arachidicola and Phytophthora capsici. Inhibition activities against SDH proved that the designed analogues were effective at the enzyme level. The SAR of these pyrazole carboxamides was studied by using the docking method. Conclusion It is possible that pyrazole carboxamides, which exhibit good activity against Sclerotinia sclerotiorum, can be further optimized as a lead compounds of carboxamide fungicides. © 2019 Society of Chemical Industry

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Design, Synthesis, and Fungicidal Evaluation of Novel Pyrazole-furan and Pyrazole-pyrrole Carboxamide as Succinate Dehydrogenase Inhibitors

Cited by 55 publications

References 26 publications

Studies on the novel pyridine sulfide containing SDH based heterocyclic amide fungicide

Studies on the novel pyridine sulfide containing SDH based heterocyclic amide fungicide

In silico studies of novel pyrazole-furan and pyrazole-pyrrole carboxamide as fungicides against Sclerotinia sclerotiorum

Novel 4‐pyrazole carboxamide derivatives containing flexible chain motif: design, synthesis and antifungal activity

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