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

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

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Understanding the Effects of Ligand Configuration on Protoporphyrinogen IX Oxidase with Rationally Designed 3-(N-Phenyluracil)but-2-enoates

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(15), P. 8401 - 8414

Published: April 8, 2024

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a promising target for green herbicide discovery. However, the ligand configuration effects on PPO activity were still poorly understood. Herein, we designed 3-(N-phenyluracil)but-2-enoates using our previously developed active fragments exchange and link (AFEL) approach synthesized series of novel compounds with nanomolar ranges Nicotiana tabacum (NtPPO) inhibitory potency herbicidal potency. Our systematic structure–activity relationship investigations showed that E isomers displayed improved bioactivity than their corresponding Z isomers. Using molecular simulation studies, found relatively lower entropy change could sample more stable binding conformation to receptor density functional theory (DFT) calculations higher chemical reactivity electronic potential Compound E-Ic emerged as optimal compound Ki value 3.0 nM against NtPPO, exhibiting broader spectrum weed control saflufenacil at 37.5–75 g ai/ha also safe maize 75 ai/ha, which be considered lead further development.

Language: Английский

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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

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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

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β-Cyclodextrin-optimized supramolecular nanovesicles enhance the droplet/foliage interface interactions and inhibition of succinate dehydrogenase (SDH) for efficient treatment of fungal diseases

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Sept. 20, 2024

Language: Английский

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Evaluation of Novel Pyridine-Based Compounds Integrating Bioactive Amide and Hydrazide Groups as a Potential Fungicide Agent

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

Published: Feb. 13, 2025

A series of novel pyridine-based compounds integrating bioactive amide and hydrazide groups were designed synthesized through an active group splicing strategy. The fungicidal bioassays indicated that several showed remarkable broad-spectrum inhibitory activity. Notably, compound A5 displayed satisfactory in vitro activity against Fusarium graminearum, Magnaporthe oryzae, Rhizoctonia solani, Colletotrichum gloeosporioides, Botrytis cinerea, Sclerotinia sclerotiorum, Alternaria sp., Physalospora piricola, with EC50 values 2.53, 2.84, 1.64, 7.59, 4.67, 5.50, 2.84 μg mL-1, respectively. Additionally, also promising vivo preventive efficiency F. graminearum R. solani at 100 mL-1. Preliminary investigation the mechanism demonstrated differentially expressed genes differential metabolites treated 10 mL-1 exhibited notable enrichment pathways associated lipid metabolism, potentially linking to plasma membrane contraction observed by TEM. Furthermore, assess environmental compatibility A5, its toxicity zebrafish, hydrolysis rates different pH buffers, effects on growth wheat seedlings evaluated. These findings will provide substantial theoretical guidance for development new environmentally friendly fungicides.

Language: Английский

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Evaluating AutoGrow4 - an open-source toolkit for semi-automated computer-aided drug discovery.

Expert Opinion on Drug Discovery, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: April 29, 2025

Drug discovery is a long and expensive process characterized by high failure rate. To make this more rational efficient, scientists always look for new better ways to design novel ligands target of interest. Among different approaches, de novo ones gained popularity in the last decade, thanks their ability efficiently explore chemical space increasing reliability generating high-quality compounds. Autogrow4 open-source software drug that generates given exploiting combination genetic algorithm molecular docking calculations. In present paper, authors dissect program's usefulness limitations compounds from pharmacodynamic pharmacokinetic perspective. Specifically, article examines all reported applications Autogrow code literature (as retrieved Scopus database) release its first version 2009 present. hands an expert modeler, useful tool ligand design. Its modular codebase offers many protocol customization features. The main downsides are limited control over features generated bias toward weight

Language: Английский

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Discovery of a Class of Novel Succinate Dehydrogenase Inhibitors Containing a Coumarin Structure

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

Published: May 7, 2025

Succinate dehydrogenase (SDH) has emerged as a highly promising target in modern agricultural research, playing crucial role developing environmentally friendly and efficient fungicides for combating pathogens. This study presents the discovery of novel class SDH inhibitors (I-III) incorporating coumarin segments achieved through an active fragment swapping linking strategy. Fungicidal activity assays revealed that several compounds within this series demonstrate significant inhibitory effects against tested fungal strains. Through comprehensive structure-activity relationship studies, compound N-(1-((3-butyl-4-methyl-2-oxo-2H-chromen-7-yl)oxy)propan-2-yl)-3-(difluoromethyl)-N-methoxy-1-methyl-1H-pyrazole-4-carboxamide (IIk) exhibited potent various species. Notably, it demonstrated superior efficacy S. sclerotiorum with EC50 value 1.14 μg/mL, outperforming commercial control agent thifluzamide (EC50 = 4.90 μg/mL). Molecular docking simulations indicated hydrophobic interactions serve primary binding mechanism between ligand SDH. Intriguingly, IIk displayed dual functionality, not only acting effective fungicide but also promoting growth wheat seedlings Arabidopsis thaliana, resulting increased plant biomass. Preliminary investigations into its growth-promoting suggest enhances nitrate reductase activity, thereby facilitating growth.

Language: Английский

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Green synthesis and antifungal activities of benzothiazole derivatives containing α-trifluoromethyl tertiary alcohol and coumarin moiety

Results in Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 102387 - 102387

Published: May 1, 2025

Language: Английский

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Discovery of Novel (5-Mercapto-4-phenyl-4H-1,2,4-triazol-3-yl)methyl Phenyl Carbamate as a Potent Phytoene Desaturase Inhibitor through Scaffold Hopping and Linker Modification

Journal of Agricultural and Food Chemistry, Journal Year: 2024, Volume and Issue: 72(34), P. 18898 - 18908

Published: Aug. 15, 2024

Phytoene desaturase (PDS) is a key rate-limiting enzyme in the carotenoid biosynthesis pathway. Although commercial PDS inhibitors have been developed for decades, it remains necessary to develop novel with higher bioactivity. In this work, we used scaffold hopping and linker modification approaches design synthesize series of compounds (

Language: Английский

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