含香豆素的吡咯并[2,3-d]嘧啶衍生物的合成及生物活性研究
收稿日期: 2023-01-31
修回日期: 2023-03-15
网络出版日期: 2023-05-25
基金资助
山东省高校科技计划(J16LC52); 济南市“高校20条”项目(引进创新团队)(2020GXRC043); 齐鲁师范学院青年博士支持计划(QBJH19-0038)
Synthesis and Biological Activity of Novel Pyrrolo[2,3-d]pyrimidine Derivatives Containing Coumarin
Received date: 2023-01-31
Revised date: 2023-03-15
Online published: 2023-05-25
Supported by
Shandong Provincial Higher Educational Science and Technology Program(J16LC52); Jinan University and the Institute Innovation Program(2020GXRC043); Young Doctor Support Program of Qilu Normal University(QBJH19-0038)
为了寻找结构新颖、活性较好的抗肿瘤化合物, 设计并合成了一系列新型的含香豆素的吡咯并[2,3-d]嘧啶衍生物, 并用核磁共振波谱(NMR)和高分辨质谱(HRMS)等方法对化合物结构进行表征. 采用四甲基偶氮唑盐(MTT)法测定了目标化合物对大鼠胶质瘤细胞(C6)、人黑色素瘤细胞(A375)和人口腔鳞癌细胞(FaDu)的抑制活性. 结果显示7-[7-(2-氟苯基)-5-(4-甲氧基苯基)-7H-吡咯并[2,3-d]嘧啶-4-氧基]-4-甲基香豆素(II1)、7-[7-(2-氟苯基)-5-(4-氟苯基)-7H-吡咯并[2,3-d]嘧啶-4-氧基]-4-甲基香豆素(II4)、7-[7-(3-氟苯基)-5-(4-甲氧基苯基)-7H-吡咯并[2,3-d]嘧啶-4-氧基]-4-甲基香豆素(III1)、7-[7-(3-氟苯基)-5-(4-氯苯基)-7H-吡咯并[2,3-d]嘧啶-4-氧基]-4-甲基香豆素(III3)和7-[7-(3-氟苯基)-5-(4-氟苯基)-7H-吡咯并[2,3-d]嘧啶-4-氧基]-4-甲基香豆素(III4)对C6细胞具有较好的抑制活性, 优于阳性对照药Imatinib, 其中化合物II4的抑制活性最好, IC50为9.60 μmol/L; 化合物I2对FaDu细胞抑制活性最好, IC50为38.61 μmol/L, 优于阳性对照药顺铂.
曹瑞霞 , 贾玉萍 . 含香豆素的吡咯并[2,3-d]嘧啶衍生物的合成及生物活性研究[J]. 有机化学, 2023 , 43(9) : 3304 -3311 . DOI: 10.6023/cjoc202301028
In order to search for new structural anti-tumor drugs, a series of novel pyrrolo[2,3-d]pyrimidine derivatives containing coumarin were synthesized and evaluated for their inhibitory activities against rat glioma cell (C6), human melanoma cell (A375) and oral squamous cell (FaDu) by using methyl thiazolyl tetrazolium (MTT) assay. These chemical structures were well characterized by nuclear magnetic resonance (NMR) and high-resolution mass spectra (HRMS) spectroscopic methods. 7-[7-(2-Fluorobenzyl)-5-(4-methoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methylchromen-2-one (II1), 7-[7-(2-fluo- robenzyl)-5-(4-fluorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methyl-chromen-2-one (II4), 7-[7-(3-fluorobenzyl)-5-(4- methoxy-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methyl-chromen-2-one (III1), 7-[5-(4-chlorophenyl)-7-(3-fluoroben- zyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methyl-chromen-2-one (III3) and 7-[7-(3-fluorobenzyl)-5-(4-fluorophenyl)-7H- pyrrolo[2,3-d]pyrimidin-4-yloxy]-4-methyl-chromen-2-one (III4) had better inhibitory activity against C6 cells than imatinib, compound II4 showed the most potent inhibitory activity against C6 cells with the IC50 values of 9.60 μmol/L. Compounds I2 had better inhibitory activity against FaDu cells than cisplatin, IC50 was 38.61μmol/L.
Key words： coumarin; synthesis; anticancer
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