Targeting tubulin protein to combat fungal disease: Design, synthesis, and its new mechanistic insights of benzimidazole hydrazone derivatives

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 140226 - 140226

Опубликована: Янв. 1, 2025

Язык: Английский

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

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

Опубликована: Фев. 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.

Язык: Английский

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Discovery of α-Methylene-γ-Butyrolactone Derivatives with Hydrazide Moieties as Novel Fungicidal Agents

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

Опубликована: Апрель 10, 2025

To discover novel fungicides with unique structures, a series of α-methylene-γ-butyrolactone derivatives were designed and synthesized by incorporating flexible amide or hydrazide chain through active substructure splicing linker modification strategies. Bioassay assessments demonstrated that certain hydrazide-containing compounds have potent fungicidal efficacy. Notably, compound 7IIj exhibited broad-spectrum antifungal activity, EC50 values as low 0.179, 0.301, 0.647, 0.549, 0.789 mg/L against Rhizoctonia solani, Physalospora piricola, Botrytis cinerea, Gaeumanomyces graminis, Valsa mali, respectively. In vivo experiments confirmed the effective activity 7IIj, showing an inhibitory rate 69.7% V. mali on apple twigs at 200 mg/L. Additionally, concentration 100 mg/L, significant protective curative effects R. solani rice plants. Research mechanism action revealed could disrupt hyphal morphology, induce reactive oxygen species (ROS) accumulation, affect mitochondrial membrane potential (MMP), interfere respiratory metabolism binding to complex II. Molecular docking analysis showed interactions TRP 173, TYR 58, ARG 43 in succinate dehydrogenase (SDH) site, resembling mode fluxapyroxad. These findings suggest holds SDH inhibitor for agricultural disease control.

Язык: Английский

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Evaluation of natural l‐phenylalanine‐derived Amidohydrazide derivatives in ensuring agriculture production against phytopathogenic fungi^†

Pest Management Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 22, 2025

Abstract BACKGROUND Ensuring food security is fundamental to national and an important guarantee for global peace development. The use of fungicides represents effective strategy in safeguarding sufficient supply against phytopathogenic fungi; however, given the escalating pathogen resistance, there urgent need develop new, highly efficient, environmentally friendly green fungicides. RESULTS In this study, 24 novel amidohydrazide derivatives were designed synthesized by incorporating bioactive amide hydrazide groups into natural l ‐phenylalanine. bioassays revealed that certain compounds exhibited remarkable inhibitory activity agricultural pathogenic fungi, with compound A21 particularly displaying exceptional vitro vivo fungicidal Rhizoctonia solani . Scanning electron microscopy (SEM) transmission (TEM) observations showed treatment induced significant morphological changes R. mycelia, including cell membrane contraction. Transcriptomic analysis indicated differentially expressed genes (DEGs) treated significantly enriched pathways related carbohydrate metabolism lipid metabolism, relative expression representative DEGs was further validated quantitative real‐time polymerase chain reaction (qRT‐PCR). increase ergosterol content suggested may counteract drug stress enhancing biosynthesis. Toxic assessment demonstrated zebrafish exposed had survival rates 90% at 1 μg mL −1 60% 10 within 72 h. Additionally, hydrolysis behavior different pH buffers these displayed rapid 9.18 buffer, while maintaining relatively high stability 4.01 6.86 buffers. CONCLUSION Amidohydrazide have excellent efficacy hold great promise as a pharmacophore development new fungicides, thereby ensuring security. © 2025 Society Chemical Industry.

Язык: Английский

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Discovery, Optimization, and Biological Evaluation of Novel Pyrazol-5-yl-phenoxybenzamide Derivatives as Potent Succinate Dehydrogenase Inhibitors

Journal of Agricultural and Food Chemistry, Год журнала: 2024, Номер 72(31), С. 17608 - 17616

Опубликована: Июль 24, 2024

The diphenyl ether molecular pharmacophore has played a significant role in the development of fungicidal compounds. In this study, variety pyrazol-5-yl-phenoxybenzamide derivatives were synthesized and evaluated for their potential to act as succinate dehydrogenase inhibitors (SDHIs). bioassay results indicate certain compounds display remarkable broad-spectrum antifungal activities. Notably, compound 12x exhibited vitro activities against Valsa mali, Gaeumannomyces graminis, Botrytis cinerea, with EC50 values 0.52, 1.46, 3.42 mg/L, respectively. These lower or comparable those Fluxapyroxad (EC50 = 12.5, 1.93, 8.33 respectively). Additionally, showed promising Sclerotinia sclerotiorum 0.82 mg/L) Rhizoctonia solani 1.86 mg/L), albeit than 0.23 0.62 mg/L). Further vivo experiments demonstrated possess effective protective V. mali S. at concentration 100 inhibition rates 66.7 89.3%, comparison, 29.2 96.4% sclerotiorum, Molecular docking analysis revealed that interacts SDH through hydrogen bonding, π-cation, π–π interactions, providing insights into probable mechanism action. Furthermore, greater binding energy enzyme inhibitory activity (ΔGcal −46.8 kcal/mol, IC50 1.22 compared ΔGcal −41.1 8.32 Collectively, our suggest could serve lead more potent SDHIs crop protection.

Язык: Английский

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Synthesis, solid state molecular structures, and cyclic voltammetry of five-coordinate perchlorate manganese porphyrins and a benzamide derivative

Journal of Coordination Chemistry, Год журнала: 2024, Номер unknown, С. 1 - 15

Опубликована: Дек. 26, 2024

We report the synthesis and characterization of two perchlorate manganese porphyrins obtained from reactions tetra-phenyl based porphyrin chloride precursors, (T(p-Cl)PP)MnCl (T(p-Cl)PP = 5,10,15,20-tetra-p-chlorophenylporphyrinato dianion) (TPP)MnCl (TPP 5,10,15,20-tetraphenylporphyrinato dianion), with excess silver perchlorate. A further reaction between (TPP)Mn(OClO3) benzamide was performed, resulting in formation a six-coordinate derivative, (TPP)Mn(O=C(NH2)Ph)(OClO3). The complexes were characterized by UV-Vis IR spectroscopy, as well single-crystal X-ray crystallography. molecular structures (T(p-Cl)PP)Mn(OClO3) (TPP)Mn(O=C(NH2)Ph)(OClO3) reveal monodentate O-binding to center. intermolecular interactions within crystalline packing both investigated using Hirshfeld surface analysis. In addition, redox behavior studied through cyclic voltammetry THF.

Язык: Английский

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