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研究论文

新型曲酸-硫醚衍生物的设计、合成及抗菌活性研究

吕洁1, 宋佳2, 阳欣燕1, 丘栩宁1, 李凯文1, 袁紫亮1,*, 任彦荣1,*, 李停停2,*   

  1. 1重庆第二师范学院生物与化学工程学院 重庆 400067;
    2贵州大学绿色农药全国重点实验室 贵阳 550025
  • 收稿日期:2026-04-02 修回日期:2026-05-29
  • 基金资助:
    重庆市科卫联合中医药科研项目(No. 2026ZYQN02), 重庆市自然科学基金创新发展联合基金项目((No. CSTB2023NSCQ-LZX0171)及重庆第二师范学院项目(No. BSRC2024070, No. 2025XJQNXZTJ05)资助.

Design, Synthesis, and Antibacterial Activity of Novel Kojic Acid-Thioether Derivatives

Lv Jie1, Song Jia2, Yang Xinyan1, Qiu Xuning1, Li Kaiwen1, Yuan Ziliang1,*, Ren Yanrong1,*, Li Tingting2,*   

  1. 1Department of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, China.;
    2State Key Laboratory of Green Pesticide, Guizhou University, Guiyang 550025, China.
  • Received:2026-04-02 Revised:2026-05-29
  • Contact: *E-mail: yuan-zi-liang@outlook.com; renyr@cque.edu.cn; litt8293@163.com
  • Supported by:
    Traditional Chinese Medicine Research Program of Chongqing Science and Health (No. 2026ZYQN023), the Chongqing Natural Science Foundation Innovation and Development Joint Fund Project (No. CSTB2023NSCQ-LZX0171), and the University-level Project of Chongqing University of Education (No. BSRC2024070, No. 2025XJQNXZTJ05).

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为了研发具有抗水稻白叶枯病菌（Xanthomonas oryzae pv. oryzae, Xoo）活性的先导化合物,本研究在曲酸结构中引入具有生物活性的硫醚片段进行修饰,设计并合成了18种新型曲酸-硫醚衍生物。所有目标化合物的结构均经核磁共振氢谱（1H NMR）和碳谱（13C NMR）确证,含氟衍生物的结构还经氟谱（19F NMR）确证。体外抗菌活性结果表明,多个衍生物（3a、3b、3c、3e、3j和3o）对Xoo均表现出优异的抗菌活性。其中,衍生物3c抗菌活性最好（EC50 = 5.22 mg/L）,其活性显著优于商品对照药剂叶枯唑（20.82 mg/L）和噻菌铜（89.77 mg/L）。构效关系（SAR）分析表明,苯环上引入对位取代的吸电子基团对增强抗菌活性至关重要。分子对接结果显示,化合物3c与关键氨基酸残基形成了氢键和π-卤素相互作用。因此,化合物3c可作为研发新型抗菌剂的候选化合物。

关键词: 曲酸-硫醚衍生物, 抗菌活性, 构效关系, 分子对接

To develop novel antibacterial agents against Xanthomonas oryzae pv. oryzae (Xoo), 18 new kojic acid-thioether derivatives were designed and synthesized through structural modification of kojic acid by incorporating bioactive thioether fragments. The structures of target derivatives were identified by 1H NMR and 13C NMR spectroscopy, and those of fluorine-containing derivatives were additionally confirmed by 19F NMR spectroscopy. The in vitro anti-Xoo activity evaluation revealed that several derivatives (3a, 3b, 3c, 3e, 3j, and 3o) exhibited significant inhibitory activity. Compound 3c (para-bromo substituted) showed the most potent activity (EC50 = 5.22 mg/L), which significantly exceeded those of the controls bismerthiazol (BT, EC50 = 20.82 mg/L) and thiodiazole copper (TC, EC50 = 89.77 mg/L). Structure-activity relationship analysis indicated that electron-withdrawing substituents and para-substitution on the phenyl ring are crucial for enhancing anti-Xoo activity. Molecular docking results indicated that compound 3c forms hydrogen bonds and π‑halogen interactions with key amino acid residues. These results demonstrate that compound 3c is a promising novel anti-Xoo agent.

Key words: Kojic acid-thioether derivatives, Antibacterial activity, Structure-activity relationship, Molecular docking