白杨素水杨酸酯类衍生物的合成及其对肝癌和胃癌细胞活性的研究

发布时间：2019-04-26 20:50

【摘要】：目的:为增强黄酮类化合物白杨素的抗癌活性,本课题以白杨素为先导化合物,设计并合成一类白杨素水杨酸酯酚醚类衍生物,并对其抗癌活性进行了初步的探讨,以期待得到具有更高效、低毒的抗癌先导化合物,为研究探索开发新的抗癌药物提供理论依据方法:本课题选用具有较好抗癌活性的天然黄酮类化合物白杨素作为先导化合物,通过醚化反应以不同长度的二溴烷烃作为中间碳链,偶联不同的水杨酸甲酯或水杨酸乙酯化合物,合成了一系列白杨素水杨酸酯类衍生物。采用四甲基偶氮唑蓝(MTT)法检测所合成的白杨素水杨酸酯类衍生物对体外培养的人胃癌MGC-803细胞及人肝癌HepG2细胞增殖的抑制作用。结果:本文通过在黄酮类化合物白杨素的7位活性羟基上以不同长度的碳链作为中间链偶联一系列不同的含卤素水杨酸酯化合物,设计合成了一系列白杨素偶联水杨酸酯类衍生物,得到了共计18个未见文献报道的新化合物。所有目标化合物结构均通过熔点、核磁共振氢谱、质谱表征确认其结构。MTT法对所合成白杨素偶联水杨酸酯类衍生物的细胞增殖实验结果表明,白杨素水杨酸酯类化合成对HepG2细胞和MGC-803细胞增殖有不同程度的抑制作用,合成的白杨素水杨酸酯类衍生物5c、6a、6c、7a、7c、8b、9a、9b对HepG2细胞的生长活性具有较好的抑制作用,均超过阳性对照药物5-FU。化合物5a、6b、6c、9b、10a、10b对MGC-803细胞的抑制增殖作用较好,这6个白杨素水杨酸酯衍生物强于母体化合物白杨素。其中化合物6c、10a、10b对MGC-803细胞的抑制增殖作用强于阳性对照药物5-FU。结论:本课题设计合成了18个未见文献报道的白杨素水杨酸酯类衍生物,初步评估了所合成的白杨素水杨酸酯类衍生物的抑制细胞增殖作用,部分化合物展现良好的抗癌活性,对于进一步开发白杨素类抗癌药物提供了新的思路。
[Abstract]:Objective: in order to enhance the anticancer activity of flavonoid compound poplar, a class of salicylate phenolic ether derivatives was designed and synthesized, and its anticancer activity was discussed. In order to obtain a more efficient, low toxicity anticancer lead compound, to provide a theoretical basis for the research and development of new anticancer drugs: in this subject, the natural flavonoid compound with good anticancer activity is chosen as the lead compound, and the natural flavonoid compound with good anticancer activity is chosen as the lead compound. A series of salicyl salicylate derivatives were synthesized by etherification reaction using dibromoalkanes of different lengths as intermediate carbon chains coupled with different methyl salicylate or ethyl salicylate compounds. The inhibitory effects of salicyl salicylate derivatives on the proliferation of human gastric cancer MGC-803 cells and human hepatoma HepG2 cells cultured in vitro were detected by tetramethylazo blue (MTT) assay. Results: a series of halogen-containing salicylate compounds were coupled with different length of carbon chains on the 7-position active hydroxyl groups of the flavonoids. A series of salicylate derivatives were designed and synthesized, and 18 new compounds were obtained. The structures of all the target compounds were confirmed by melting point, nuclear magnetic resonance (NMR) and mass spectrometry (MS). The results of cell proliferation of salicylsalicylate derivatives by MTT assay showed that: Salicylic acid ester synthesis can inhibit the proliferation of HepG2 cells and MGC-803 cells to some extent. The derivatives of salicylic acid esters are 5c, 6a, 6c, 7a, 7c, 8b, 9a, 5c, 6a, 6c, 7a, 7c, 8b, 9a, respectively. 9b had a good inhibitory effect on the growth activity of HepG2 cells, which was more than that of the positive control drug 5? Compounds 5a, 6b, 6c, 9b, 10a, 10b inhibited the proliferation of MGC-803 cells, and these six salicylate derivatives were stronger than the parent compound salicylate. Compound 6c, 10a, 10b inhibited the proliferation of MGC-803 cells more strongly than that of 5? Conclusion: in this study, 18 salicylate derivatives were designed and synthesized, and the inhibitory effects of salicylate derivatives on cell proliferation were evaluated. Some of the compounds showed good anticancer activity. It provides a new idea for the further development of poplar anticancer drugs.
【学位授予单位】：南华大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R914.5;R96

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