Novel Pyrazole Acyl(thio)urea Derivatives Containing a Biphenyl Scaffold as Potential Succinate Dehydrogenase Inhibitors: Design, Synthesis, Fungicidal Activity, and SAR

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(5), P. 2512 - 2525

Published: Jan. 29, 2024

As part of a program to discover novel succinate dehydrogenase inhibitor fungicides, series new pyrazole acyl(thio)urea compounds containing diphenyl motif were designed and synthesized. Their structures confirmed by

Language: Английский

---

Novel 5-(Trifluoromethyl)-1,2,4-oxadiazole-Based Pyrimidin-4-ether Histone Deacetylase Inhibitors for Controlling Rust Disease: Design, Synthesis, Activity, and Structure–Activity Relationship

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Rust disease, an important plant pathogen, can lead to reduced crop or fruit production. Trifluoromethyloxadiazole (TFMO) is a class of histone deacetylase inhibitors (HDACs). Herein, series 5-(trifluoromethyl)-1,2,4-oxadiazole (TFMO)-based pyrimidin-4-ether derivatives were designed and synthesized. Antirust bioassay results TFMOs showed that some them possessed excellent activities against rust pathogens, such as Puccinia sorghi, Phakopsora pachyrhizi, rubigo. The most active compound, 3-(5-(((6-(difluoromethyl)pyrimidin-4-yl)oxy)methyl)thiophen-2-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole (XII6), exhibited 50% control P. pachyrhizi at 0.780 mg/L, which was significantly better than the commercial fungicide azoxystrobin (0%) same concentration. field trial indicated compound effect rubigo 116 g a.i./ha. acute toxic XII6 has low toxicity. Furthermore, enzyme activity strong, nonselective HDAC inhibitor. Finally, structure–activity relationship established, XII6-HDAC binding mode carried out based on crystal structure hHDAC1, hHDAC4, hHDAC6. This work provided for further optimization.

Language: Английский

---

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

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(28), P. 15427 - 15448

Published: July 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.

Language: Английский

---

(NH₄)₂S₂O₈ promoted tandem radical cyclization of quinazolin-4(3H)-ones with oxamic acids for the construction of fused quinazolinones under metal-free conditions

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(11), P. 2241 - 2251

Published: Jan. 1, 2024

A novel cascade radical addition/cyclization reaction of non-activated olefins and oxamic acids has been proposed.

Language: Английский

---

Discovery of novel piperidine‐containing thymol derivatives as potent antifungal agents for crop protection

Pest Management Science, Journal Year: 2024, Volume and Issue: 80(10), P. 4906 - 4914

Published: May 30, 2024

Abstract BACKGROUND Plant fungal diseases pose a significant threat to crop production. The extensive use of chemical pesticides has led growing environmental safety risks and pesticide resistance various plant pathogens. Therefore, it is an urgent task explore novel eco‐friendly fungicidal agents with high efficacy combat infection. RESULTS In this study, we rationally designed series thymol derivatives by incorporation the sulfonamide moiety evaluated their biological activities against pathogenic fungi. bioassay results underscored remarkable in vitro antifungal activity compounds 5m 5t Phytophthora capsici ( P. ), EC 50 values 8.420 8.414 μ g/mL, respectively. Their efficacies were superior that widely used commercial fungicides azoxystrobin (AZO, 20.649 g/mL) cabendazim (CAB, 251.625 g/mL). Furthermore, compound 5v exhibited excellent Sclerotinia sclerotiorum S. value 12.829 significantly outperforming AZO (63.629 vivo bioassays demonstrated impactful , achieving over 98% curative protective at concentration 200 g/mL. Further mechanistic investigations unveiled induced mycelial shrinkage collapse resulting organelle damage accumulation antioxidant enzyme activity. CONCLUSION prepared shall encourage further exploration as promising candidate develop for protection. © 2024 Society Chemical Industry.

Language: Английский

---

Design, Synthesis, Antifungal Activity, and Action Mechanism of Pyrazole-4-carboxamide Derivatives Containing Oxime Ether Active Fragment As Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(20), P. 11308 - 11320

Published: May 9, 2024

The dearomatization at the hydrophobic tail of boscalid was carried out to construct a series novel pyrazole-4-carboxamide derivatives containing an oxime ether fragment. By using fungicide-likeness analyses and virtual screening, 24 target compounds with theoretical strong inhibitory effects against fungal succinate dehydrogenase (SDH) were designed synthesized. Antifungal bioassays showed that compound E1 could selectively inhibit in vitro growth R. solani, EC50 value 1.1 μg/mL superior agricultural fungicide (2.2 μg/mL). observations by scanning electron microscopy (SEM) transmission (TEM) demonstrated reduce mycelial density significantly increase mitochondrial number mycelia cytoplasm, which similar phenomenon treated boscalid. Enzyme activity assay had significant effect SDH from IC50 3.3 μM (7.9 μM). mode action further analyzed molecular docking dynamics simulation studies. Among them, hydrogen bonds more SDH-E1 complex than SDH-boscalid complex. This research on strategy benzene ring for constructing pyrazole-4-carboxamides fragment provides unique thought design new antifungal drugs targeting SDH.

Language: Английский

---

Design, Synthesis, and Biological Evaluation of Novel Aryl Sulfonamide Derivatives as Potential Succinate Dehydrogenase Inhibitors Targeting Phytopathogenic Fungi

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

In our pursuit of novel succinate dehydrogenase inhibitor (SDHI) fungicides for agriculture, we replaced the traditional amide structure with a sulfonamide framework and introduced various heterocyclic aromatic rings at sulfonamide's termini. This strategy yielded 30 synthesized compounds, which were screened antifungal activity against eight phytopathogenic fungi. The biological assay results demonstrated that several target compounds exhibited significant in vitro activity. Notably, compound 2f showed remarkable Valsa mali an EC50 value 0.56 mg/L, outperforming Boscalid (EC50 = 1.79 mg/L). vivo experiments revealed provided protection to apple fruits, comparable Boscalid. SEM analysis 3e disrupted morphology fungal hypha analysis, suggested terminal polyhalogen-substituted pyridine moieties might be pivotal regions influencing their efficacy. Molecular docking binding mode SDH. Furthermore, detailed SDH inhibition assays confirmed potential (IC50 2.51 μM) as prospective inhibitors. RNA transcriptomic indicated application could influence gene expression fungi, thereby exerting defensive effect plant pathogenic Consequently, shows promise developing efficient agrochemical fungicide.

Language: Английский

---

Design, Synthesis, and Anti-Oomycete and Antifungal Activities of Novel Paeonol Derivatives Containing a Pyrazole Ring

Journal of Agricultural and Food Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Paeonol is the main active ingredient in Chinese medicinal herb peony root bark. To discover biorational natural product-based fungicides, 25 paeonol derivatives (5a-y) containing a pyrazole ring were designed and synthesized by ingeniously introducing five-membered heterocyclic ring, their structures well characterized 1H NMR, 13C high-resolution mass spectrometer (HRMS), m.p. The stereochemical configurations of six target compounds, 5c, 5f, 5g, 5o, 5s, 5v, unambiguously subjected to single-crystal X-ray diffraction. Furthermore, we evaluated bioactivities these compounds as anti-oomycete antifungal agents against two serious agricultural diseases, Phytophthora capsici Fusarium graminearum. Among all tested (1) nine 5b-d, 5r, 5u, 5w displayed promising P. capsici, with EC50 values ranging from 22.1 34.5 mg/L, protective effect vivo further confirmed above results. (2) Six 5k, 5m, 5t, 5w, 5x F. graminearum, 38.2 86.0 mg/L. Moreover, some interesting results structure-activity relationships also observed. this study pave way for design, synthesis, development potential botanical crop protection.

Language: Английский

---

Synthesis, fungicidal activity and molecular docking of novel pyrazole-carboxamides bearing a branched alkyl ether moiety

Bioorganic & Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 108, P. 129813 - 129813

Published: May 22, 2024

Language: Английский

---

Discovery of Benzothiazol-2-ylthiophenylpyrazole-4-carboxamides as Novel Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(32), P. 17802 - 17812

Published: Aug. 2, 2024

Succinate dehydrogenase (SDH) has been considered an ideal target for discovering fungicides. To develop novel SDH inhibitors, in this work, 31 benzothiazol-2-ylthiophenylpyrazole-4-carboxamides were designed and synthesized using active fragment exchange a link approach as promising inhibitors. The findings from the tests on antifungal activity indicated that most of compounds displayed remarkable inhibition against fungi tested. Compound

Language: Английский

---