A bioactivity-oriented modification strategy for SDH inhibitors with superior activity against fungal strains

Líu, Hao; Xia, Dong-Guo; Hu, Rui; Wang, Wei; Cheng, Xiang; Wang, Aili; Zhang, Qin; Lv, Xian-Hai

doi:10.1016/j.pestbp.2019.11.024

Cited by 26 publications

(33 citation statements)

References 23 publications

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“…Compounds 7d and 7l (Figures 6A—6D) showed three visible strong hydrogen bonds with the side chain amino acid residues of Tyr58 and Trp173, which play a crucial role in maintaining fungicidal activity. [ 38‐39 ] In addition, the residues ARG43, HIS216, ILE40 and PRO169 are also critical in a continuous belt of hydrophobic interactions encircling pyrazole and benzene ring of compounds 7l and 7d . Obviously, compound 7r (Figures 6E and 6F) also showed strong interactions with SDH protein in the same active pocket and formed two hydrogen bonds with amino acid residues of Tyr58 and Trp173, which maintain its certain fungicidal activity.…”

Section: Resultsmentioning

confidence: 99%

Synthesis, Bioactivity Evaluation,3D‐QSAR, and Molecular Docking of Novel Pyrazole‐4‐carbohydrazides as Potential Fungicides Targeting Succinate Dehydrogenase

et al. 2021

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Main observation and conclusion To screen novel antifungal agents targeting the succinate dehydrogenase (SDH), a series of pyrazole‐4‐carbohydrazides were rationally designed, synthesized, and characterized under the guidance of the structures of succinate dehydrogenase inhibitors (SDHIs). Bioassay results in vitro indicated that most of the target compounds exhibited excellent activity against Rhizoctonia solani (R. solani), Fusarium graminearum (F. graminearum), Botrytis cinerea (B. cinerea) and Colletotrichum capsica (C. cinerea). Compounds 7d, 7l, 7t and 7x were identified as the most promoting candidates, and their anti‐F. graminearum EC50 values were as low as 0.56, 0.47, 0.46 and 0.49 μg/mL, respectively, presenting the similar antifungal activity as that of the commonly used fungicide carbendazim (0.43 μg/mL). The 3D‐QSAR models were built for a systematic structure‐activity relationship profile to explore more potent pyrazole‐4‐carbohydrazides as novel fungicides. Molecular docking of 7d, 7l and 7r with SDH was performed to reveal the binding modes in active pocket and analyze the interactions between the molecules and the SDH protein.

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Section: Resultsmentioning

confidence: 99%

Synthesis, Bioactivity Evaluation,3D‐QSAR, and Molecular Docking of Novel Pyrazole‐4‐carbohydrazides as Potential Fungicides Targeting Succinate Dehydrogenase

et al. 2021

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“…Shanghai, China). All the 1 H and 13 C NMR spectra were measured on Agilent DD2 600 Hz spectrometer with CDCl 3 or DMSO-d 6 as the solvent and tetramethylsilane as the internal standard. Chemical shifts were reported in ppm (⊐).…”

Section: Reagents and Equipmentmentioning

confidence: 99%

“…19,20 [3,4-d]pyrimidin-4-one derivatives were synthesized and the general pathways were outlined in Scheme 2. The chemical structures of all synthesized compounds were confirmed by MS, 1 H NMR, and 13 C NMR and characterization data were supplied in the Supporting Information.…”

Section: Toxicity Test To Italian Beesmentioning

confidence: 99%

“…11 In recent years, our team mainly focused on the optimization of the amine moiety on SDHIs. In our previous work, boscalid being used as a lead compound, we reported two potential novel SDH inhibitors 3l 12 and 5IV-d, 13 which displayed good antifungal activities.(Fig. 1) In order to continue exploring novel potential SDHIs with unique skeleton and improved fungicidal activity, we initiated a structural optimization campaign focusing on 4th of pyrazole.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and biological activity of novel Pyrazolo[3,4‐d]pyrimidin‐4‐one derivatives as potent antifungal agent

Wang

Cheng

Cui

et al. 2021

Pest Management Science

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BACKGROUND: To promote the discovery and development of new fungicide with novel scaffolds or modes of action, a series of novel 5-(2-chloroethyl)-1-phenyl-6-(pyridin-4-yl)-1,5-dihydro-4H-pyrazolo [3,4-d]pyrimidin-4-one derivatives were synthesized, and evaluated for their antifungal activities.RESULTS: The bioassay data showed that compound 8IIId (EC 50 = 1.93 mg L −1 ) is superior to boscalid (EC 50 = 6.71 mg L −1 ) against Valsa mali. We introduced chiral groups on the structure of 8IIId, and two chiral configurations were respectively synthesized, which are 8Vc and 8Vd. Surprisingly, 8Vc showed significant antifungal activities against Valsa mali and Physalospora piricola with EC 50 values of 0.22 and 0.55 mg L −1 . Physiological and biochemical studies showed that the primary action mechanism of compound 8Vc on Valsa mali may involve changing mycelial morphology and increasing cell membrane permeability.CONCLUSION: These results demonstrated that 8Vc could be further modified as fungicide and provided a valuable reference for antifungal agents with pyrazolo [3,4-d]pyrimidin-4-one skeleton.

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“…Plant diseases caused by fungi can significantly affect the growth and development of crops such as potato, soybean, and rice, and reduce the yield (20% perennial yield losses and 10% postharvest losses) of crop plants globally [1][2][3][4]. Meanwhile, fungal plant diseases also cause fresh fruit yield loss due to the shortening of storage times and secretion of fungal toxins that can damage human health [5,6].…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Crystal Structure, and Fungicidal Activity of Two Fenclorim Derivatives

Xiong

Feng-Pei

2020

Crystals

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Two fenclorim derivatives (compounds 6 and 7) were synthesized by linking active sub-structures using fenclorim as the lead compound. The chemical structures of the two compounds were confirmed by NMR spectroscopy, high resolution mass spectrometry, and X-ray diffraction analysis. Their fungicidal activity against six plant fungal strains was tested. Compounds 6 and 7 both crystallized in the monoclinic system, with a P21/c space group (a = 8.4842(6) Å, b = 24.457(2) Å, c = 8.9940(6) Å, V = 1855.0(2) Å3, Z = 4) and Cc space group (a = 10.2347(7) Å, b = 18.3224(10) Å, c = 7.2447(4) Å, V = 1357.50(14) Å3, Z = 4), respectively. The crystal structure of compound 6 was stabilized by C–H···N and C–H···O hydrogen bonding interactions and N–H···N hydrogen bonds linked the neighboring molecules of compound 7 to form a three-dimensional framework. Compound 6 displayed the most excellent activity, which is much better than that of pyrimethanil against Botrytis cinerea in vivo. Additionally, compound 6 exhibited greater in vitro activity against Pseudoperonospora cubensis compared to that of pyrimethanil. Moreover, compound 7 exhibited strong fungicidal activity against Erysiphe cichoracearum at 50 mg/L in vitro, while pyrimethanil did not. Compounds 6 and 7 could be used as new pyrimidine fungicides in the future.

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A bioactivity-oriented modification strategy for SDH inhibitors with superior activity against fungal strains

Cited by 26 publications

References 23 publications

Synthesis, Bioactivity Evaluation,3D‐QSAR, and Molecular Docking of Novel Pyrazole‐4‐carbohydrazides as Potential Fungicides Targeting Succinate Dehydrogenase

Synthesis, Bioactivity Evaluation,3D‐QSAR, and Molecular Docking of Novel Pyrazole‐4‐carbohydrazides as Potential Fungicides Targeting Succinate Dehydrogenase

Synthesis and biological activity of novel Pyrazolo[3,4‐d]pyrimidin‐4‐one derivatives as potent antifungal agent

Design, Synthesis, Crystal Structure, and Fungicidal Activity of Two Fenclorim Derivatives

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