Design and development of pyrazol‐5‐ylbenzamide derivatives containing chiral oxazoline moiety as fungicides based on molecular docking

Pest Management Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

Development of novel chiral antifungal agents for effective control plant pathogens is urgently needed. In this study, a series pyrazol-5-yl-benzamide derivatives containing oxazoline moiety were rationally designed and developed based on molecular docking. The in vitro assay results indicated that compounds (rac)-4h (R1 = Et), (S)-4 h S-Et) (R)-4 R-Et) exhibited remarkable activities against Valsa mali with median concentration (EC50) values 0.24, 0.06 1.08 mg/L, respectively. Preliminary structure-activity relationships (SARs) revealed the modification substituent group at significantly affected target compounds. Furthermore, (S)-4h (87.5%) (R)-4h (84.3%) vivo protective comparable to tebuconazole V. mali. Subsequent docking analysis, succinate dehydrogenase (SDH) enzyme inhibition assays dynamic (MD) simulations verified potential class could be SDH helped explain large difference (R)-4h. Confocal laser scanning microscopy (CLSM) electron (SEM) observations confirmed these two severely disrupted mycelial morphology Theoretical calculation studies provided some insight into subsequent such derivatives. Resistance frequency showed treatments less likely produce resistant fungal strains than tebuconazole. Meanwhile, no apparent toxicity Apis mellifera L. Therefore, are candidates development fungicides crop protection. © 2025 Society Chemical Industry.

Language: Английский

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Antifungal activity and biocompatibility assessment with molecular docking and dynamic simulations of new pyrazole derivatives

BMC Biotechnology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 6, 2025

Abstract Background Because of their many bioactivities, which include psychoanalytic, antifungal, antihypertensive, anti-inflammatory, and antiviral properties, pyrazoles derivatives are attracting interest in pharmacology medicine, the pressing need for novel fungicides is increased lessened by growing microbiological resistance illnesses to recognized antibiotics. Objective The current work validates results pyrazole binding sites as potent antifungals investigating antifungal agents. biocompatibility was assessed using an HFB4 normal human skin cell line. Methods evaluated line findings were confirmed molecular docking. investigation against 4 fungal pathogens: Aspergillus flavus ATCC 9643, A. niger 11414, Rhizopus oryzae 96382, Penicillium chrysogenum 10106. Results Among 20 different Pyrazole derivatives, 3b most effective compound 11414 9643 with IZDs AIs 32.0 mm (1.10) 30.0 (1.0), respectively. Followed 10b scored 28 P. 10106, While R. 96382 exhibited all compounds. study found that showed 100% activity between 1000 500 μg/ml, 50% at doses 250 no action a dose 125 μg/ml studied pathogenic strains. completely safe IC 50 obtained. effectiveness several compounds targets through docking studies. highlighted 3b, 3g, 3h, 10b, 7 , 12 displayed strong energies, effectively engaging active key proteins various fungi such FDC1 uridine diphosphate N -acetylglucosamine (UDP-GlcNAc) Adenosine 5′-phosphosulfate kinase . These interactions encompassed diverse bonding types, suggesting these compounds’ potential hinder enzyme demonstrate notable properties. Additionally, computational ADMET “Absorption–distribution–metabolism–excretion–toxicity” analysis revealed adherence Lipinski’s rules, indicating favorable physicochemical characteristics. dynamic simulations 5’-phosphosulfate UDP-N-acetylglucosamine also demonstrated formation stable complexes values Root Mean Square Deviation (RMSD), Fluctuation (RMSF), Solvent Accessible Surface Area (SASA), Radius Gyration (Rg). support ongoing therapeutic development projects. Conclusion agent. energies suggest drug development.

Language: Английский

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Design, synthesis, and mechanism study of novel natural-based isoquinolone derivatives as potential antifungal agents

Journal of Asian Natural Products Research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 14

Published: April 21, 2025

A series of isoquinolone compounds Ia-Iq containing amide moiety were rationally designed and synthesized based-on alkaloids. Their structures confirmed by 1H NMR,13C NMR HRMS. Most the title showed medium to excellent antifungal activity in vitro at 50 mg/L. Especially, EC50 Im (13.155 mg/L) against P. piricola was slightly better than chlorothalonil (14.323 mg/L). The vivo on apples comparable chlorothalonil. Preliminary mechanistic exploration illustrated that strongly damage mycelium morphology. Furthermore, molecular electrostatic potential docking analysis revealed could interact with residues SDH via hydrogen bond.

Language: Английский

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Novel Naphthyl and Phenyl Maleimide Derivatives: Molecular Design, Systematic Optimization, Antifungal Evaluation, and Action Mechanism

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

Published: April 29, 2025

A systematic optimization strategy, as an effective screening approach for new antifungal compounds, was implemented to rationally construct novel naphthyl and phenyl maleimide derivatives. The structures of molecules A32 B6 were further confirmed by single-crystal X-ray diffraction. in vitro activity evaluation showed that the target compound obtained structure exhibited excellent inhibition (EC50 = 0.59 μg/mL) against Rhizoctonia solani, which better than control agent dimethachlone (1.21 μg/mL). Further vivo experiments on rice leaves potted plants R. solani at 200 μg/mL possessed outstanding protective efficiency compared dimethachlone. mycelium morphology observation SEM indicated (25 severely damaged surface mycelium, accordance with increased result cell membrane permeability assay. MD simulations molecular docking analysis revealed compounds A1 have a similar binding mode active pocket plasma H+-ATPases (PMA1) reference fungicide fluoroimide. In particular, there more hydrogen bonds protein complex complexes This research constructing derivatives strategy provides practical way find leads, thereby developing fungicides.

Language: Английский

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Direct Trifluoromethylselenolations of electron-rich aromatic(hetero) rings with N-trifluoromethylselenolating saccharin

Organic & Biomolecular Chemistry, Journal Year: 2024, Volume and Issue: 22(37), P. 7707 - 7714

Published: Jan. 1, 2024

A novel, easily synthesizable, shelf-stable electrophilic trifluoromethylselenolating reagent,

Language: Английский

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