Design, Synthesis, and Antifungal Activities of Novel Potent Fluoroalkenyl Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(26), С. 14535 - 14546

Опубликована: Июнь 21, 2024

The development of new fungicide molecules is a crucial task for agricultural chemists to enhance the effectiveness fungicides in production. In this study, series novel fluoroalkenyl modified succinate dehydrogenase inhibitors were synthesized and evaluated their antifungal activities against eight fungi. results from

Язык: Английский

---

Recent Advances in Design and Development of Diazole and Diazine Based Fungicides (2014–2023)

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(28), С. 15427 - 15448

Опубликована: Июль 5, 2024

With fungal diseases posing a major threat to agricultural production, the application of fungicides control related is often considered necessary ensure world's food supply. The search for new bioactive agents has long been priority in crop protection due continuous development resistance against currently used types active compounds. Heterocyclic compounds are an inseparable part core structures numerous lead compounds, these rings constitute pharmacophores significant number developed over past decade by agrochemists. Among heterocycles, nitrogen-based play essential role. To date, diazole (imidazole and pyrazole) diazine (pyrimidine, pyridazine, pyrazine) derivatives make up important series synthetic fungicides. In recent years, many reports have published on design, synthesis, study fungicidal activity scaffolds, but there was lack comprehensive classified review nitrogen-containing scaffolds. Regarding this issue, here we reviewed articles families. current review, molecules synthesized so far based size ring.

Язык: Английский

---

Discovery of Novel Acethydrazide-Containing Flavonol Derivatives as Potential Antifungal Agents

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(31), С. 17229 - 17239

Опубликована: Июль 25, 2024

In this study, a series of novel hydrazide-containing flavonol derivatives was designed, synthesized, and evaluated for antifungal activity. the in vitro assay, most target compounds exhibited potent activity against seven tested phytopathogenic fungi. particular, compound C32 showed best Rhizoctonia solani (EC50 = 0.170 μg/mL), outperforming carbendazim 0.360 μg/mL) boscalid 1.36 μg/mL). Compound C24 excellent Valsa mali, Botrytis cinerea, Alternaria alternata with EC50 values 0.590, 0.870, 1.71 μg/mL, respectively. The vivo experiments revealed that were potential agricultural antifungals. 3D quantitative structure–activity relationship (3D-QSAR) models used to analyze relationships these compounds. analysis results indicated introducing appropriate electronegative groups at position 4 benzene ring could effectively improve anti-R. mechanism scanning electron microscopy transmission analyses disrupted normal growth hyphae by affecting structural integrity cell membrane cellular respiration. Furthermore, succinate dehydrogenase (SDH) inhibitory (IC50 8.42 μM), surpassing SDH fungicide 15.6 μM). molecular dynamics simulations docking suggested can occupy active site form strong interactions key residues SDH. Our findings have great aiding future research on plant disease control agriculture.

Язык: Английский

---

Novel heterocyclic amide derivatives containing a diphenylmethyl moiety: systematic optimizations, synthesis, antifungal activity and action mechanism

Pest Management Science, Год журнала: 2024, Номер unknown

Опубликована: Сен. 30, 2024

Abstract BACKGROUND The development of fungicides with low cross resistance, high efficacy and resistance plays a central role in protecting crops, reducing yield losses, improving quality maintaining global food security. Based on this important role, after systematic optimization strategy, novel heterocyclic amide derivatives bearing diphenylmethyl fragment were screened, synthesized verified the spectrographic x‐ray diffraction analysis. RESULTS In study, aforementioned obtained compound B19 that was measured for antifungal activity against Rhizoctonia solani (median effective concentration, EC 50 = 1.11 μg mL −1 ). Meanwhile, anti‐ R. protective effect (79.34%) evaluated vivo at 100 , which is comparable to control agent fluxapyroxad (80.67%). Thence, morphological observations revealed induced mycelium disruption shrinking, mitochondrial number reduction apoptosis acceleration, consistent results membrane potential cell permeability. Further investigations found target enzyme SDH, exerted fluorescence quenching dynamic curves similar commercialized SDHI fluxapyroxad. Additionally, research by molecular docking MD simulations demonstrated had binding mode acting surrounding residues SDH active pocket offluxapyroxad. CONCLUSION above containing moiety are promising scaffolds targeting fungi provide valuable leads develop new inhibitors. © 2024 Society Chemical Industry.

Язык: Английский

---

Scaffold Hopping from Dehydrozingerone: Design, Synthesis, and Antifungal Activity of Phenoxyltrifluoromethylpyridines

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(11), С. 5345 - 5345

Опубликована: Июнь 2, 2025

In response to the urgent need for innovative fungicides ensure food security and safety, a series of twenty-three novel trifluoromethylpyridine compounds were designed synthesized using scaffold hopping strategy derived from dehydrozingerone. This approach involved converting α, β-unsaturated ketone moiety into pyridine ring. Bioassay results indicated that majority these exhibited promising in vitro antifungal activity, particularly against Rhizoctonia solani Colletotrichum musae. Notably, compound 17 showed highest efficacy broad-spectrum with median effective concentrations (EC50) ranging 2.88 9.09 μg/mL. Phenoxytrifluoromethylpyridine derivatives, including 17, superior activity compared benzyloxytrifluoromethylpyridine derivatives. vivo tests revealed both 23 moderate control effects C. The degradation half-lives bananas determined be 176.9 h 94.8 h, respectively, indicating stability their structures environment. Molecular docking studies interacts succinate dehydrogenase, offering valuable insights structural optimization 23.

Язык: Английский

---

Discovery of Novel Pyrazole β-Ketonitrile Derivatives as Broad Spectrum SDHI Fungicides by Introducing a Flexible Motif

Journal of Agricultural and Food Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Июнь 3, 2025

Scaffold optimization plays a critical role in the exploration of fungicides with improved potency and an expanded spectrum. In this study, series novel pyrazole β-ketonitrile derivatives were rationally designed identified as potent broad-spectrum succinate dehydrogenase inhibitor fungicides, through modifying molecular flexibility via flexible methylene motif. After stepwise modifications, compounds A21, A24, A33 displayed broad spectrum antifungal activities vitro against Fusarium graminearum, Sclerotinia sclerotiorum, Rhizoctonia solani. Especially, compound (EC50 = 0.356 μg/mL) exhibited comparable fungicidal F. graminearum to positive control pydiflumetofen 0.104 μg/mL). greenhouse assay, moderate vivo protective effects rice blast at 100 μg/mL, significant protection cucumber powdery mildew 50 wheat scab 200 μg/mL. The (SDH) inhibitory assay revealed that are SDH inhibitors concentration values 0.123, 0.0317, 0.0709 μM, respectively. Docking results demonstrated H-bonds cation-π interactions between residues Trp173, Tyr91, Arg46 important for binding within SDH. Our findings improvement scaffold is effective approach explore SDHIs.

Язык: Английский

---

Novel Insecticidal Pyridylhydrazono Derivatives Identified via Scaffold Hopping and Conformation Regulation Strategies

Chemistry & Biodiversity, Год журнала: 2024, Номер 21(12)

Опубликована: Авг. 26, 2024

Abstract Insect transient receptor potential vanilloid (TRPV) channels are critical targets for insecticides. In this study, various scaffold‐hopping strategies were employed in the rational design of pyridylhydrazono derivatives as insect TRPV modulators. Insecticidal bioassay demonstrated that initial target compounds exhibited lower insecticidal activity compared to pymetrozine, with optimal compound B3 exhibiting a mortality rate 53.3 % against Aphis craccivora at 400 mg L −1 . Conformation analysis indicated high energy barrier required transition from lowest‐energy conformation active may be key factor contributing reduced activities compounds. Further structural optimizations aimed reducing through binding mode‐based regulation led identification 4‐(3′‐pyridylhydrazono)pyrazol‐5‐one C1 and C2 These barriers improved activity, moderate 66.3 75.7 A. , respectively. findings provide valuable insights future research on discovery modulators have significant implications development more effective agricultural

Язык: Английский

---

Comprehensive Overview of the Amide Linker Modification in the Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(47), С. 26027 - 26039

Опубликована: Ноя. 14, 2024

Succinate dehydrogenase inhibitors (SDHIs) have become one of the most important classes agrochemical fungicides. According to data from FRAC, resistance risk for SDHIs had reached up medium and even high. In general, chemical structure mainly contained three fragments: an acid core, a hydrophobic tail, amide linker, corresponding modification directions each fragment. Among them, linker (ALM) has research hotspot design novel fungicides in recent years. We presented here detailed review on ALM strategy past decade, some them entered market. their structures, were classified into four parts: (1) linked aliphatic chain between bond (2) introducing substituents replacing hydrogen atom bond, (3) reverse extending (4) changed with other bioisosteres. Moreover, structure–activity relationship interaction mechanism ALM-SDHI SDH discussed. This aims provide global perspective development SDHIs, as well suggestions food safety management.

Язык: Английский

---

Novel SDH Inhibitors as Antifungal Leads: From Azobenzene Derivatives to the 1,2,4-Oxadiazole Compounds

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 22, 2024

Azo-incorporating was reported to be an effective strategy for increasing SDH inhibitory activity but poor in vivo control effects. Herein, the azo-incorporated compounds were structurally optimized retain a preferential conformation by replacing azo bond with their bioisosteres. Interestingly, 1,2,4-oxadiazole compound

Язык: Английский

---

Triazole Sulfonamide Derivates: Inhibitors of the bc₁ Complex to Control Cucumber Downy Mildew

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 22, 2024

Cucumber downy mildew (CDM), caused by Pseudoperonospora cubensis, is a destructive disease that affects greenhouse cucumbers and causes significant losses for growers. Amisulbrom, triazole sulfonamide fungicide targeting the Qi site in bc1 complex, has shown potential effectively combating CDM. However, its detailed binding mode with target unclear. In this study, three-dimensional (3D) structure of complex from P. cubensis was built, interaction amisulbrom investigated integrating molecular docking, dynamics, mechanics/Poisson−Boltzmann surface area (MM/PBSA) methods. Based on Pc-bc1 scaffold hopping strategy performed, compounds 11a–o 12a–v were designed. Among them, compound 12g showed excellent fungicidal properties against CDM field trials. The present work indicated oxime ether moiety could be further optimized better results. Furthermore, to serve as lead search new Qi-site inhibitors complex.

Язык: Английский

---