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Design, synthesis, and antifungal activity evaluation of novel 2-cyano-5-oxopentanoic acid derivatives as potential succinate dehydrogenase inhibitors

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Abstract

Two series of novel 2-cyano-5-oxopentanoic acid derivatives (1a−l, 2a−l) were designed, synthesized, and characterized by IR, 1H NMR, 13C NMR, and HRMS. Their in vitro antifungal activity against five plant pathogenic fungi were then assessed, including Gibberella zeae, Helminthosporium maydis, Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum. Single crystals of compound 1c were determined and crystallized in the orthorhombic system with space group Fdd2. The inhibitory rate and the median effect concentrations (EC50) of compounds 1c, 1g, 1k, and 2i were better than carbendazim against S. sclerotiorum at 20 µg/mL. Meanwhile, the half inhibitory concentrations (IC50) of compounds 1c, 1g, 1k, and 2i against succinate dehydrogenase (SDH) and their score in molecular docking were both lower than carbendazim, indicating that these four compounds have stronger antifungal activities and affinities than carbendazim. Therefore, we conclude that compounds 1c, 1g, 1k, and 2i might be potential succinate dehydrogenase inhibitors (SDHIs).

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Acknowledgements

This study was supported by the National Key R&D Program of China (2018YFD0900904) and the Chengdu Science and Technology Project (No. 2018-YF05-00970-SN). We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

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Authors and Affiliations

  1. Guangdong Provincial Key Laboratory of Emergency Test for Dangerous Chemicals, Institute of Analysis, Guangdong Academy of Sciences (China National Analytical Center, Guangzhou), Guangzhou, 510070, China

    Xue-song Wang & Mi-jun Peng

  2. School of Science, Xihua University, Chengdu, 610039, China

    Xiao-rong Tang

  3. Pearl River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510380, China

    Yong-zhan Mai

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Wang, Xs., Tang, Xr., Peng, Mj. et al. Design, synthesis, and antifungal activity evaluation of novel 2-cyano-5-oxopentanoic acid derivatives as potential succinate dehydrogenase inhibitors. Med Chem Res 31, 94–107 (2022). https://doi.org/10.1007/s00044-021-02818-2

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