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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Investigation of the Antifungal Activity and Preliminary Mode of Action of Novel 2-(1H-Indol-2-yl)-1,3,4-oxadiazole Derivatives against Botrytis cinerea

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

Published: Feb. 27, 2025

The discovery of novel leads and new targets is an important approach to address the issue fungicide resistance by development. indole skeleton has been widely utilized in agrochemicals due its unique biological activity. YZK-C22 a potent pyruvate kinase inhibitor with high antifungal Several were developed based on YZK-C22. Inspired these, [1,2,4]triazino[4,5-a]indol-1(2H)-one derivatives designed using hopping strategy; however, these compounds exhibited moderate fungicidal Unexpectedly, 2-(1H-indol-2-yl)-1,3,4-oxadiazole formed under controlled reaction conditions showed significantly higher Compounds 6c, 6d, 6f, 6j excellent activity vitro, EC50 values ranging from 0.120 0.310 μg/mL against Botrytis cinerea, more than commercial pyrimethanil (EC50 = 0.990 μg/mL). In field trials at 540 720 g active ingredient (ai)/hm2, compound 6c 81.46 86.58% efficacy B. that rate ai/hm2 (70.46%). affinity constants 6d cinerea lower Higher but implies may work as prodrugs or have different mode action. Thus, are worth being further investigated.

Language: Английский

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Three-Dimensional Polyglycerol–PEG-Based Hydrogels as a Universal High-Sensitivity Platform for SPR Analysis

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

We developed a three-dimensional (3D) polyglycerol–poly(ethylene glycol)-based hydrogel as new biosensing matrix for affinity analysis by surface plasmon resonance to enable high loading of ligands small molecule while lacking carbohydrate structure reduce nonspecific binding. The was synthesized cross-linking polyglycerol functionalized with carboxylate and maleimide groups dithiolated poly(ethylene glycol) thiol-click chemistry. demonstrated that the coating enabled immobilization capacity biomolecules led less Here, degree carbonic anhydrase II resulting binding signal acetazolamide were increased factor 5 compared standard CMD sensors (CM5), comparable specialized maximum (CM7). This capacity, combined reduced due missing structure, presents an innovative broad application range (SPR) experiments since no current commercial SPR biosensor combines these two key features.

Language: Английский

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Fungicidal Activity of Carboxamides Containing Spiropiperidinyl-α-methylene-γ-butyrolactones Targeting Oxysterol Binding Protein

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

Published: April 1, 2025

Oxysterol binding protein (OSBP) is a new target for oomycide development. To find more fungicidal active compounds targeting OSBP, series of carboxamides containing spiropiperidinyl-α-methylene-γ-butyrolactone and heterocyclic carboxylic acids were rationally designed synthesized by using computer-aided pesticide design method. The in vitro bioassay found that compound 5o showed broad-spectrum activity with EC50 values falling between 0.50 20.85 μg/mL against Phytophthora capsici Fusarium verticillioides, respectively, which was potent than 7c natural lead xanthatin. Compound also 44% vivo efficacy Pseudoperonospora cubensis, even at concentration 0.5 μg/mL. Fluorescence quenching microscale thermophoresis determination suggested bound to Osh4p stronger interactions oxathiapiprolin. RNA sequencing analysis discovered the ergosterol (ERG) gene cluster ribosome biogenesis eukaryotes downregulated. as good candidate OSBP deserving further studies.

Language: Английский

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