阿魏酸衍生物的合成及其抗肿瘤活性研究

Study on Synthesis and Antitumor Activity of Ferulic Acid Derivatives

关键词:  阿魏酸衍生物  合成  抗肿瘤  表皮生长因子受体

Key words:  ferulic acid derivatives  synthesis  anti-tumor  epidermal growth factor

摘要:

目的 设计、合成了一系列含有喹唑啉结构的阿魏酸衍生物，并对其抗肿瘤活性进行研究。方法 基于拼接原理，将阿魏酸与喹唑啉进行结合，并对喹唑啉6位进行修饰得到目标化合物，采用CCK-8法测试目标化合物对肺癌细胞A549的抗肿瘤活性，利用分子对接技术对目标化合物与表皮生长因子受体的结合模式进行模拟。结果 目标化合物的结构经HRMS(ESI)、¹H-NMR进行确证；体外抗肿瘤活性结果表明化合物11d、11f、12d和12g的IC₅₀低于阳性药吉非替尼，11c的IC₅₀值与吉非替尼相当。结论 化合物11d(IC₅₀=3.09 μmol·L^-1)对肺癌细胞A549抗肿瘤活性较强，值得深入研究。

Abstract:

OBJECTIVE To design and synthesize a series of ferulic acid derivatives containing quinazoline structure, and to study their antitumor activity. METHODS Based on the principle of splicing, ferulic acid was combined with quinazoline, and the 6-position of quinazoline was modified to obtain the target compound. The anti-tumor activity of the target compound against lung cancer cell A549 was tested by CCK-8 method. Molecular docking technology was used to simulate the binding mode of the target compound and epidermal growth factor receptor. RESULTS The structure of the target compound was confirmed by HRMS (ESI) and ¹H-NMR. The in vitro antitumor activity results showed that the IC₅₀ of compounds 11d, 11f, 12d and 12g were lower than the positive drug of gefitinib, and the IC₅₀ of 11c was comparable to gefitinib. CONCLUSION Compound 11d (IC₅₀=3.09μmol·L^-1) has strong antitumor activity against lung cancer cell A549, which is worthy of further study.