新型含金刚烷结构抗肿瘤药物小分子的合成及生物活性研究

发布时间：2018-05-13 18:30

本文选题：金刚烷 + 抗肿瘤活性　；参考：《长春工业大学》2017年硕士论文

【摘要】：在过去的十年间,癌症的发病率和死亡率在逐年增加,这就使得我们不得不重视这一重大疾病,进而使得癌症药物的研发和治疗迫在眉睫;由于传统的放疗、化疗和药物治疗具有一定的毒副作用,有待我们进一步研究开发高效低毒的抗肿瘤药物;尽管已知的小分子抑制剂的数量在不断增加,但只有少数抑制剂通过临床前和早期临床开发应用。在这次的研究中,我们将进一步合成小分子抗癌抑制剂。本文主要是合成一系列新颖的含有金刚烷结构的抗肿瘤药物小分子,以及研究它们对多种癌细胞系的抑制活性。合成主要是以1-溴代金刚烷为起始原料,经过典型的付克烷基化反应、维蒂希反应、还原反应、NBS溴代反应、偶联反应等多步反应合成目标化合物。经质谱(MS)、核磁(~1H-NMR)、(~(13)C-NMR)、红外(FT-IR)以及高分辨质谱(HRMS)证实其结构。通过MTS法对6个目标化合物进行人肝癌细胞SMMC7721、乳腺癌细胞MCF-7、宫颈癌细胞Hela、肺癌细胞A549的增值抑制活性研究,部分化合物表现出较好的活性。化合物8f对这些细胞的总体抑制作用明显强于其它化合物;其中目标化合物8e只对特定的人肝癌细胞表现出较好的抑制活性,其抑制浓度为1.6μmol;所合成的金刚烷类似物为新型的抗肿瘤化合物提供了一定的参考价值,该类化合物可能在靶向抗肿瘤药物研发方面具有较好的研究前景。
[Abstract]:In the past decade, the incidence and mortality of cancer have been increasing year by year, which makes us pay more attention to this major disease, which makes the development and treatment of cancer drugs urgent. Chemotherapy and drug therapy have some toxic side effects, and we need to further study and develop highly effective and low-toxic antitumor drugs, although the number of known small molecular inhibitors is increasing. But only a few inhibitors are developed and applied preclinically and early. In this study, we will further synthesize small molecule anticancer inhibitors. In this paper, a series of novel antitumor molecules with adamantane structure were synthesized and their inhibitory activities on various cancer cell lines were studied. The target compounds were synthesized from 1-bromoadamantane by typical alkylation reaction, Wittig reaction, reduction reaction, bromination reaction, coupling reaction and so on. Its structure was confirmed by MS, 1H-NMR-1H-NMR-1H-NMR-1H-NMR-1H-NMR-IR (FT-IRIR) and HRMS (high resolution mass spectrometry). The inhibitory activity of six target compounds on human hepatoma cell line SMMC7721, breast cancer cell line MCF-7, cervical cancer cell Hela and lung cancer cell A549 was studied by MTS assay. The overall inhibitory effect of compound 8f on these cells was significantly stronger than that of other compounds, and the target compound 8e only showed good inhibitory activity on specific human hepatoma cells. The inhibitory concentration was 1.6 渭 mol, and the synthesized adamantane analogue provided a certain reference value for the novel antitumor compounds, which may have a good prospect in the research and development of targeted antitumor drugs.
【学位授予单位】：长春工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.1

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