| 引用本文: |
郭易华,黄志勇,王福东,李龙,李荣东.新型氨基酸类衍生物的设计、合成及抗肿瘤活性研究[J].湖南中医药大学学报,2022,42(1):55-62[点击复制] |
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| 新型氨基酸类衍生物的设计、合成及抗肿瘤活性研究 |
| 郭易华,黄志勇,王福东,李龙,李荣东 |
| (湖南中医药大学, 湖南 长沙 410208) |
| 摘要: |
| 目的 将氨基酸引入喹唑啉母核，探究含喹唑啉结构的氨基酸衍生物的抗肿瘤细胞增殖活性。方法 以DL-苯丙氨酸、L-苯丙氨酸、D-苯丙氨酸和3-氨基-3-苯基丙酸为原料合成关键中间体，与喹唑啉母核连接合成一系列4-苯氨基喹唑啉衍生物。采用CCK-8法测试目标化合物对非小细胞肺癌细胞（A549）的抗增殖活性。通过LeDock软件测试目标化合物与EGFR蛋白的结合效果。结果 合成了21个新型4-苯氨基喹唑啉衍生物，经1H NMR、LC-MS确证其结构。体外抗肿瘤实验结果表明，目标化合物12u与12o的抗肿瘤活性与阳性对照药吉非替尼相当。LeDock软件测试结果与体外抗肿瘤实验结果一致。结论 新型4-苯氨基喹唑啉衍生物具有抗非小细胞肺癌的作用，为进一步探究含喹唑啉的氨基酸抗肿瘤药物打下基础。 |
| 关键词: 氨基酸衍生物 喹唑啉 非小细胞肺癌 A549 细胞增殖 化学合成 |
| DOI：10.3969/j.issn.1674-070X.2022.01.011 |
| 投稿时间：2021-07-01 |
| 基金项目:湖南中医药大学药学一流学科开放基金重点项目（2021YXO1）。 |
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| Design, synthesis and antitumor activity of novel amino acid derivatives |
| GUO Yihua,HUANG Zhiyong,WANG Fudong,LI Long,LI Rongdong |
| (Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
| Abstract: |
| Objective To introduce amino acids into the quinazoline core to explore the anti-tumor cell proliferation activity of amino acid derivatives containing quinazoline structure. Methods DL-phenylalanine, L-phenylalanine, D-phenylalanine and 3-amino-3-phenylpropionic acid were used as raw materials to synthesize key intermediates, which were connected to the quinazoline core to synthesize a series 4-phenylaminoquinazoline derivatives. The CCK-8 method was used to test the anti-proliferative activity of the target compound on non-small cell lung cancer cells (A549). LeDock software was used to test the binding effect of the target compound and EGFR protein. Results 21 novel 4-phenylaminoquinazoline derivatives were synthesized, and their structures were confirmed by 1H NMR and LC-MS. The results of in vitro anti-tumor experiments showed that the antitumor activity of compound 12u and 12o was equivalent to that of the positive control drug gefitinib. The LeDock software test results were consistent with the results of in vitro anti-tumor experiments. Conclusion The novel 4-phenylaminoquinazoline derivatives have anti-non-small cell lung cancer effects, which lay the foundation for further exploration of quinazoline containing amino acid anti-tumor drugs. |
| Key words: amino acid derivatives quinazoline non-small cell lung cancer A549 cell proliferation chemical synthesis |
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