新型氨基酸类衍生物的设计、合成及抗肿瘤活性研究  

Design,synthesis and antitumor activity of novel amino acid derivatives

作　　者：郭易华 黄志勇 王福东[1] 李龙[1] 李荣东[1] GUO Yihua;HUANG Zhiyong;WANG Fudong;LI Long;LI Rongdong(Hunan University of Chinese Medicine,Changsha,Hunan 410208,China)

机构地区：[1]湖南中医药大学,湖南长沙410208

出　　处：《湖南中医药大学学报》2022年第1期55-62,共8页Journal of Hunan University of Chinese Medicine

基　　金：湖南中医药大学药学一流学科开放基金重点项目(2021YXO1)。

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。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 by1 H NMR and LC-MS. The results of in vitro anti-tumor experiments showed that the antitumor activity of compound12 u and 12 o 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.

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 

分 类 号：R284.3[医药卫生—中药学]