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Novel (Z)/(E)-1,2,4-triazole derivatives containing oxime ether moiety as potential ergosterol biosynthesis inhibitors: design, preparation, antifungal evaluation, and molecular docking

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Abstract

Inspired by the highly effective and broad-spectrum antifungal activity of ergosterol biosynthesis inhibitions, a series of novel 1,2,4-triazole derivatives containing oxime ether moiety were constructed for screening the bioactivity against phytopathogenic fungi. The (Z)- and (E)-isomers of target compounds were successfully separated and identified by the spectroscopy and single crystal X-ray diffraction analyses. The bioassay results showed that the (Z)-isomers of target compounds possessed higher antifungal activity than the (E)-isomers. Strikingly, the compound (Z)-5o exhibited excellent antifungal activity against Rhizoctonia solani with the EC50 value of 0.41 μg/mL in vitro and preventive effect of 94.58% in vivo at 200 μg/mL, which was comparable to the positive control tebuconazole. The scanning electron microscopy observation indicated that the compound (Z)-5o caused the mycelial morphology to become wizened and wrinkled. The molecular docking modes of (Z)-5o and (E)-5o with the potential target protein RsCYP51 were especially compared. And the main interactions between ligands and amino acid residues were carefully analyzed to preliminarily explain the mechanism leading to the difference of activity between two isomers. The study provided a new lead molecular skeleton for developing novel triazole fungicides targeting ergosterol biosynthesis.

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Acknowledgements

The authors gratefully acknowledge the grants from the National Natural Science Foundation of China (No. 31772209) and the Fundamental Research Funds for the Central Universities of China (No. KYTZ201604).

Funding

Funding was provided by Innovative Research Group Project of the National Natural Science Foundation of China (Grant No. 31772209), Fundamental Research Funds for the Central Universities (Grant No. KYTZ201604).

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Authors and Affiliations

  1. College of Sciences, Nanjing Agricultural University, Nanjing, 210095, China

    Shengxin Sun, Jinghua Yan, Lang Tai, Jianqi Chai, Haoran Hu, Ling Han, Aimin Lu, Chunlong Yang & Min Chen

  2. Jiangsu Key Laboratory of Pesticide Science, Nanjing Agricultural University, Nanjing, 210095, China

    Jianqi Chai, Aimin Lu, Chunlong Yang & Min Chen

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  1. Shengxin Sun
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Appendix A

Appendix A

The physical and spectroscopic data, crystal structure information and molecular docking related information of target compounds are provided in the Supporting Information. The copies of corresponding 1 H NMR, 13C NMR, 19F NMR, and HRMS spectrograms are also presented in the Supporting Information.

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Sun, S., Yan, J., Tai, L. et al. Novel (Z)/(E)-1,2,4-triazole derivatives containing oxime ether moiety as potential ergosterol biosynthesis inhibitors: design, preparation, antifungal evaluation, and molecular docking. Mol Divers 27, 145–157 (2023). https://doi.org/10.1007/s11030-022-10412-w

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