Design, synthesis, X‐ray crystal structure, and antifungal evaluation of new acetohydrazide derivatives containing a 4‐thioquinazoline moiety DOI

Guangmin Tian,

Mingyan Yi,

T F Yan

et al.

Pest Management Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 4, 2024

Abstract BACKGROUND To find efficient agricultural fungicides, 29 new 4‐thioquinazoline‐containing acetohydrazide derivatives were prepared and tested for their fungicidal properties. RESULTS All of the target compounds characterized by 1 H 13 C nuclear magnetic resonance high‐resolution mass spectrometry techniques, molecular structure compound A2 was verified single‐crystal X‐ray diffraction measurement. The experimental results revealed that many from this series had impressive inhibition efficacies in vitro against fungi. For example, A25 identified as best agent Rhizoctonia solani with an EC 50 (half‐maximal effective concentration) value 0.66 μg mL −1 , superior to those commercial fungicides chlorothalonil, carbendazim boscalid. Additionally, displayed favorable protection curative activities vivo rice sheath blight caused R . Antifungal mechanistic studies on indicated exerted its strong anti ‐R effects probably through fungal succinate dehydrogenase activity [half‐maximal inhibitory concentration (IC ) = 4.88 μ m ] impairment cell membrane integrity, based enzymatic bioassays, docking studies, scanning transmission electron microscopy observations. CONCLUSION Acetohydrazide containing 4‐thioquinazoline moiety potential be employed lead developing more near future. © 2024 Society Chemical Industry.

Language: Английский

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

Weilong Xu,

Mian Du

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(26), P. 14535 - 14546

Published: June 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

Language: Английский

Citations

6
Recent Advances in Design and Development of Diazole and Diazine Based Fungicides (2014–2023) DOI
Ebrahim Saeedian Moghadam,

Fahimeh Bonyasi,

Bahareh Bayati

et al.

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

Citations

6
Discovery of Novel Acethydrazide-Containing Flavonol Derivatives as Potential Antifungal Agents DOI
Hongyi Chen,

Zunyun Jiang,

T. He

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(31), P. 17229 - 17239

Published: July 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.

Language: Английский

Citations

4
Comprehensive Overview of the Amide Linker Modification in the Succinate Dehydrogenase Inhibitors DOI
Li Zeng, Qi Chen,

Ge Wei

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(47), P. 26027 - 26039

Published: Nov. 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.

Language: Английский

Citations

2
Novel Insecticidal Pyridylhydrazono Derivatives Identified via Scaffold Hopping and Conformation Regulation Strategies DOI
Xiaoyang Li, Cong Zhou, Wu‐Lin Yang

et al.

Chemistry & Biodiversity, Journal Year: 2024, Volume and Issue: 21(12)

Published: Aug. 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

Language: Английский

Citations

2
Novel heterocyclic amide derivatives containing a diphenylmethyl moiety: systematic optimizations, synthesis, antifungal activity and action mechanism DOI
Feng Peng,

Jianqi Chai,

Yue Xie

et al.

Pest Management Science, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 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.

Language: Английский

Citations

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

Qinglong Yuan,

Hongti Zhang

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 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

Language: Английский

Citations

1
Triazole Sulfonamide Derivates: Inhibitors of the bc1 Complex to Control Cucumber Downy Mildew DOI
Ying Dong, Xiaoyan Guan, Z. L. Guan

et al.

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

Citations

1
The resistance mechanism of B_P225F and B_H272R mutations in succinate dehydrogenase in Botrytis cinerea DOI
Jun Ma, Ying Ma, Zhaoxin Lu

et al.

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: unknown, P. 139360 - 139360

Published: Dec. 1, 2024

Language: Английский

Citations

1
Design and optimization of novel succinate dehydrogenase inhibitors against agricultural fungi based on Transformer model DOI Open Access
Yuan Zhang,

Jianqi Chai,

Ling Li

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 20, 2024

Abstract Succinate dehydrogenase inhibitors (SDHIs) are a promising class of fungicides targeting the energy production pathway pathogenic fungi. However, overuse has led to resistance, necessitating development new and effective SDHIs. This study takes Transformer model generate customized virtual library potential These candidates were then meticulously screened based on expert knowledge synthetic feasibility, ultimately yielding several pyrazole carboxamide derivatives as leads. Subsequent synthesis, antifungal activity testing, structural optimization further refined these leads into potent SDHI candidates. work marks first application generative design, establishing robust workflow for generation, screening, evaluation, structure optimization. provides one way rational design future SDHIs, not only against fungi, but potentially other agricultural pathogens well.

Language: Английский

Citations

0