高等学校化学学报2026，Vol.47Issue(7)：104-116,13.DOI:10.7503/cjcu20260072
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
Synthesis and Anti-lung Cancer Activity of 3-(1H-indol-4-yl)-1-(pyrimidin-2-yl)prop-2-en-1-one-spirooxindole Hybrid Derivatives
摘要
Abstract
Aiming to search for novel anti-lung cancer active compounds,1,3-dipoles were obtained by decarboxy-lation of isatin with sarcosine,proline and thioproline,respectively,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 means of nuclear magnetic resonance hydrogen spectrum,nuclear magnetic resonance carbon spectrum and high Resolution mass spectrometry,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 cell counting kit-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[half maximal inhibitory concentration(IC50)=(0.037±0.002)μmol/L]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],and could significantly block the cell quiescence(G0)and DNA synthesis prophase(G1)of A549/DDP cells,induce cell apoptosis and inhibit cell migration ability,its mechanism of action may be associated with the Janus kinase(JAK)and P-glycoprotein targets(P-gp).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.关键词
3-螺环氧化吲哚/嘧啶/衍生物/抗肿瘤活性Key words
3-Spirooxindole/Pyrimidine/Derivative/Antitumor activity分类
化学化工引用本文复制引用
杨俊,黄冬燕,梁光平,刘雄利..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[J].高等学校化学学报,2026,47(7):104-116,13.基金项目
贵州省卫生健康委员会科学技术基金(批准号:gzwkj[2026]134)、遵义市科技合作计划项目(批准号:[2025]238,[2024]398)和遵义医药高等专科学校科研团队建设项目(批准号:遵医专团队[2026]02号)资助. Supported by the Guizhou Provincial Health Commission Science and Technology Fund Project,China(No.gzwkj[2026]134),the Science and Technology Project of Zunyi City,China(Nos.[2025]238,[2024]398)and the Scientific research team building project of Zunyi Medical and Pharmaceutical College,China(No.[2026]02). （批准号:gzwkj[2026]134）
