高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    

3-(1H-吲哚-4-基)-1-(嘧啶-2-基)丙-2-烯-1-酮拼接螺环氧化吲哚衍生物的合成及抗肺癌活性研究

杨俊1,黄冬燕1,梁光平1,刘雄利2   

  1. 1. 遵义医药高等专科学校 2. 贵州大学, 西南药食两用资源开发利用技术国家地方联合工程研究中心
  • 收稿日期:2026-02-05 修回日期:2026-03-02 网络首发:2026-03-05 发布日期:2026-03-05
  • 通讯作者: 梁光平 E-mail:746641572@qq.com
  • 基金资助:
    贵州省卫生健康委科学技术基金(批准号: gzwkj[2026]134)和遵义市科技合作计划(批准号: [2025]238，[2024]398)资助

Synthesis and Anti-Lung Cancer Activity of 3-(1H-Indol-4-yl)-1-(Pyrimidin-2-yl)Prop-2-En-1-One-Spirooxindole Hybrid Derivatives

YANG Jun1, HUANG Dongyan1, LIANG Guangping1, LIU Xiongli2   

  1. 1. Zunyi Medical And Pharmaceutical College
    2. National ＆ Local Joint Engineering Research Center for the Exploition of Homology Resources of Medicine and Food, Guizhou University
  • Received:2026-02-05 Revised:2026-03-02 Online First:2026-03-05 Published:2026-03-05
  • Supported by:
    Supported by the Guizhou Provincial Health Commission Science and Technology Fund Project(No. gzwkj[2026]134) and the Science and Technology Project of Zunyi City(Nos.[2025]238，[2024]398)

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摘要： 为寻找新型抗肺癌活性化合物, 首次将靛红分别与肌氨酸、脯氨酸、硫代脯氨酸经脱羧得到的1, 3偶极体, 与3-(1H-吲哚-4-基)-1-(嘧啶-2-基)丙-2-烯-1-酮作为的亲偶极体, 发生1, 3偶极环加成反应共得到33个目标化合物, 其结构通过1H NMR、13C NMR 和HRMS表征, 相对构型通过X-射线单晶衍射确定; 通过CCK-8法测定目标化合物对人肺腺癌耐顺铂细胞株(A549/DDP)、人非小细胞肺癌细胞株(A549)的体外抑制活性, 该类化合物对A549、A549/DDP细胞均具有较好的抑制活性, 且对耐药株A549/DDP具有较高的选择性, 其中化合物4cj对A549/DDP表现出极佳的抑制活性(IC50 = 0.037 ± 0.002 μmol?L-1)及选择性, 是阳性对照药顺铂(IC50 = 2.496 ± 0.117 μmol?L-1)的60多倍, 可以显著地阻滞A549/DDP细胞G0/G1期, 诱导细胞凋亡, 抑制细胞迁移能力, 其作用机制可能与JAK及P-gp靶点有关. 以上结果表明化合物4cj可作为先导化合物, 继续研究开发成为高效、高选择性的抗肺癌耐药剂.

关键词: 3-螺环氧化吲哚, 嘧啶, 衍生物, 抗肿瘤活性

Abstract: Aiming to search for novel anti-lung cancer active compounds, 1,3 dipoles were obtained by decarboxylation of isatin with sarcosine, proline and thioproline respectively for the first time, and then 1,3 dipole cycloaddition reactions were carried out with 3-(1H-indol-4-yl)-1-(2-pyrimidinyl)-2-propen-1-one as the dipole philophore to obtain a total of 33 target compounds. Their structures were characterized by 1H NMR, 13C NMR and HRMS, and the relative configurations was determined by X-ray single crystal diffraction. The in vitro inhibitory activities of the target compound on cisplatin-resistant human lung adenocarcinoma cell line (A549/DDP) and human non-small cell lung cancer cell line (A549) were determined by the CCK-8. This type of compound had good inhibitory activity against both A549 and A549/DDP cells, and had high selectivity against the drug-resistant strain A549/DDP. Compound 4cj showed excellent inhibitory activity (IC50 = 0.037 ± 0.002 μmol?L-1) and selectivity against A549/DDP, which was more than 60 times that of the positive control drug cisplatin (IC50 = 2.496 ± 0.117 μmol?L-1), and could significantly block the G0/G1 phase of A549/DDP cells, induce cell apoptosis and inhibit cell migration ability, its mechanism of action may be associated with the JAK and P-gp targets. The above results indicated that compound 4cj can be used as a lead compound for further research and development into a highly efficient and selective anti-lung cancer drug.

Key words: 3-Spirooxindole; Pyrimidine, Derivatives, Antitumor activity

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