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Rational design, synthesis, and antimicrobial evaluation of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety

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Abstract

In this paper, a series of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety were constructed. The synthetic compounds were characterized by 1H NMR, 13C NMR, HRMS, and single crystal diffraction. The antimicrobial activities of title compounds against fungi (Pyricutaria oryzae Cav., Phomopsis sp., Botryosphaeria dothidea, cucumber Botrytis cinerea, tobacco Botrytis cinerea, blueberry Botrytis cinerea) and bacteria (Xanthomonas oryzae pv. oryzicola, Xoc; Xanthomonas axonopodis pv. citri, Xac) revealed these compounds possessed excellent antibacterial activity through mycelial growth rate method and turbidity method, respectively. Among them, compounds 7a, 7d, 7g, 7k, 7l, and 7n had the antibacterial inhibition rate of 90.68, 97.86, 93.61, 97.70, 97.26, and 92.34%, respectively. The EC50 values of 7a, 7d, 7g, 7k, 7l, and 7n were 58.31, 48.76, 58.50, 40.11, 38.15, and 46.99 μg/mL, separately, superior to that of positive control pesticide thiodiazole copper (104.26 μg/mL). The molecular docking simulation of compound 7l and glutathione s-transferase also confirmed its good activity. The in vivo bioassay toward Xac infected citrus leaves was also performed to evaluate the potential of compounds as efficient antibacterial reagent. Further study of antibacterial mechanism was also carried out, including extracellular polysaccharide production, permeability of bacterial membrane, and scanning electron microscope observations. The excellent antibacterial activities of these compounds provided a strong support for its application for preventing and control plant diseases.

Graphical abstract

A series of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives were constructed as potential protective reagents against Xanthomonas axonopodispv. citri, Xac.

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Acknowledgements

This work was financially supported by Guizhou Provincial Science and Technology Projects (QKH PTRC-CXTD[2022] 002), Education Department of Guizhou Province-Natural Science Research Project (QJJ[2023]042), and Science and Technology Fund Project of Guizhou (QKHJC[2020]1Z023), Guizhou Provincial Science and Technology Projects (QKHCG[2023]YB090), and Guiyang University Graduate Student Innovation Project (GYU-YJS[2021]-38).

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  1. Qiang Fei and Chunyi Liu contributed equally to this work.

Authors and Affiliations

  1. Guizhou Engineering Research Center for Characteristic Flavor Perception and Quality Control of Drug-Food Homologous Resources, Guiyang University, Guiyang, 550005, People’s Republic of China

    Qiang Fei, Chunyi Liu, Yanbi Luo, Haijiang Chen, Fengwei Ma, Su Xu & Wenneng Wu

  2. School of Food Science and Engineering, Guiyang University, Guiyang, 550005, People’s Republic of China

    Qiang Fei, Chunyi Liu, Yanbi Luo, Haijiang Chen, Fengwei Ma, Su Xu & Wenneng Wu

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Contributions

QF, CL, and YL: They proceeded the organic synthesis, bioassay, and data analysis. HC: He provided help for the design of bioassay and data analysis and wrote the manuscript. FM: He had contributed to characterization of compounds. SX and WW: They proposed the idea, analyzed the data, provided funding support, and revised the manuscript. All authors agreed with the publication.

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Correspondence to Haijiang Chen, Su Xu or Wenneng Wu.

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Fei, Q., Liu, C., Luo, Y. et al. Rational design, synthesis, and antimicrobial evaluation of novel 1,2,4-trizaole-substituted 1,3,4-oxadiazole derivatives with a dual thioether moiety. Mol Divers (2024). https://doi.org/10.1007/s11030-024-10848-2

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