Design, synthesis, crystal structure, fungicidal activity, and mechanism of action of novel thiazole-based hydrazide derivatives containing the 4-aminoquinazoline moiety

Bioorganic Chemistry, Год журнала: 2025, Номер 156, С. 108237 - 108237

Опубликована: Фев. 2, 2025

Язык: Английский

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Synthesis, antifungal activity, and molecular simulation study of nootkatone‐based thiazole‐hydrazone compounds as novel succinate dehydrogenase inhibitor

Pest Management Science, Год журнала: 2025, Номер unknown

Опубликована: Янв. 21, 2025

Plant diseases cause huge losses in agriculture worldwide every year, but the prolonged use of current commercial fungicides has led to development resistance plant pathogenic fungi. Therefore, there is an urgent need develop new, efficient, and green fungicides. Twenty-three nootkatone-based thiazole-hydrazone compounds were designed, synthesized, characterized by Fourier-transform infrared (FTIR), proton (1H) nuclear magnetic resonance (NMR), carbon-13 (13C) NMR, high-resolution mass spectrometry (HRMS). The antifungal activities results showed that all target displayed certain activity against eight tested Among them, 3a (88.7%), 3b (92.5%), 3d 3f (84.9%), 3j 3l (92.5%) comparable or superior positive control boscalid (88.7%) their inhibitory Physalospora piricola. Meanwhile, compound had half maximal effective concentration (EC50) values 18.0172, 18.8236, 16.5914, 18.5044, 16.5660 μg/mL Fusarium oxysporum f. sp. cucumerinum, Alternaria solani, Gibberella zeae, Bipolaris maydis, Colleterichum orbicalare, respectively, exhibiting outstanding broad-spectrum fungicidal activity. Moreover, a three-dimensional quantitative structure-activity relationship (3D-QSAR) study was carried out investigate between molecular structures 3a-3w Furthermore, [half (IC50) = 4.936 μmol/L] significantly better succinate dehydrogenase (SDH) than (IC50 6.631 μmol/L). possible binding mode homology-modeling built SDH, also explored docking. Target deserved further as promising candidate for novel SDH inhibitor. © 2025 Society Chemical Industry.

Язык: Английский

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

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

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

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

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Design, synthesis and antifungal activity of novel pyrazole-amide-isothiazole derivatives as succinate dehydrogenase inhibitors

Food Chemistry, Год журнала: 2024, Номер 464, С. 141465 - 141465

Опубликована: Окт. 9, 2024

Язык: Английский

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