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

Jianqi Chai,

Ling Li

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 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.

Язык: Английский

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

Weilong Xu,

Mian Du

и другие.

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

Процитировано

8
Understanding the Effects of Ligand Configuration on Protoporphyrinogen IX Oxidase with Rationally Designed 3-(N-Phenyluracil)but-2-enoates DOI

Huang-Ze Yang,

Hongyun Liu,

Sang-Hong Li

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(15), С. 8401 - 8414

Опубликована: Апрель 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.

Язык: Английский

Процитировано

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

Fahimeh Bonyasi,

Bahareh Bayati

и другие.

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

Процитировано

6
Discovery of Benzothiazol-2-ylthiophenylpyrazole-4-carboxamides as Novel Succinate Dehydrogenase Inhibitors DOI

Yan-Ming Yin,

Xiaoming Zhang,

Xiao-Yue Shang

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(32), С. 17802 - 17812

Опубликована: Авг. 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

Язык: Английский

Процитировано

6
Evaluation of Novel Pyridine-Based Compounds Integrating Bioactive Amide and Hydrazide Groups as a Potential Fungicide Agent DOI
Shuo Wang, Zhanfang Chen,

S.-H. Li

и другие.

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

Опубликована: Фев. 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.

Язык: Английский

Процитировано

0
Evaluating AutoGrow4 - an open-source toolkit for semi-automated computer-aided drug discovery. DOI
Davide Bassani, Matteo Pavan, Stefano Moro

и другие.

Expert Opinion on Drug Discovery, Год журнала: 2025, Номер unknown, С. 1 - 10

Опубликована: Апрель 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

Язык: Английский

Процитировано

0
Discovery of a Class of Novel Succinate Dehydrogenase Inhibitors Containing a Coumarin Structure DOI

Yan-Ming Yin,

Tian Chen,

Huang-Ze Yang

и другие.

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

Опубликована: Май 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.

Язык: Английский

Процитировано

0
Green synthesis and antifungal activities of benzothiazole derivatives containing α-trifluoromethyl tertiary alcohol and coumarin moiety DOI Creative Commons

Shengfei Jiang,

Jianqi Xu, Zhuang Wu

и другие.

Results in Chemistry, Год журнала: 2025, Номер unknown, С. 102387 - 102387

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
β-Cyclodextrin-optimized supramolecular nanovesicles enhance the droplet/foliage interface interactions and inhibition of succinate dehydrogenase (SDH) for efficient treatment of fungal diseases DOI Creative Commons

Deng-Xuan Guo,

Li Song, Jinghan Yang

и другие.

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Сен. 20, 2024

Язык: Английский

Процитировано

3
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 DOI
Di Zhang, Chunxue Wang, Yichi Zhang

и другие.

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(34), С. 18898 - 18908

Опубликована: Авг. 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 (

Язык: Английский

Процитировано

2