Z-2，3-二芳基丙烯腈及噻唑并三唑酮类衍生物的设计合成及其生物活性研究

发布时间：2018-06-12 07:27

  本文选题：白藜芦醇 + 2　； 参考：《延边大学》2017年硕士论文

【摘要】：癌症是威胁人类健康的一种恶性疾病,仅在中国,每年就有200万人因癌症死去,目前根治癌症的方式为手术治疗,但由于许多种肿瘤细胞如白血病,淋巴癌等全身性癌症、以及已经侵蚀周围组织的肿瘤无法进行手术,而化疗对身体危害极大,许多肿瘤患者不仅要承受肿瘤本身的疼痛,而且要承受化疗药物对身体造成的伤害,所以,寻找到活性高毒性小的抗肿瘤药物是世界学者面临的共同难题。本论文通过查阅资料,发现从植物中提取的白藜芦醇具有抗菌、抗炎、抗肿瘤等多种生物活性,但由于结构中含有三个酚羟基结构,导致其自身稳定性较差,并且活性较低,所以将白藜芦醇作为先导化合物,其结构中的羟基进行甲基化,并引入氰基结构合成一些列2,3-二芳基丙烯腈类化合物,所合成的化合物通过MTT等方法检测其体外抗肿瘤活性。根据文献报道,含氮杂环结构是一种易与生物体结合的杂环,其中1,2,4-三氮唑为一种公认的重要活性基团,同时,噻唑酮类化合物也是一种抗肿瘤活性基团,所以将两者进行拼合,作为桥连键,合成一系列三唑并噻唑酮类衍生物,并通过生物活性的测试,检测其抗肿瘤活性。所有化合物经~1HNMR和~(13)C NMR,IR等进行结构确证。结果显示,2,3-二芳基丙烯腈类化合物具有较好的抗肿瘤活性,其中,化合物4d[(Z)-2-(3,5-二甲氧基苯基)-3-(4-溴基苯基)]丙烯腈与4p[(Z)-2-(3,5-二甲氧基苯基)-3-(乙氧基苯基)丙烯腈)]在HeLa中的抗肿瘤活性强于紫杉醇,而且在正常细胞中有较低的毒性,表现出很好的选择性抗癌作用。该类化合物能够抑制肿瘤细胞的迁移作用,并能有效的抑制细胞停留在G2/M期。三唑并噻唑酮类衍生物也表现出不同程度的抗肿瘤活性,其中5k[(Z)-5-(3-乙酰氧基基亚苄基)-2-(3-吡啶基)噻唑并[3,2-b][1,2,4]三氮唑-6(5H)-酮]活性最佳,其在AGS细胞中的IC50值为20.3±8.3μM,是一种有效的抗肿瘤药物。
[Abstract]:Cancer is a malignant disease that threatens human health. In China alone, 2 million people die of cancer every year. At present, surgical treatment is the way to cure cancer. However, because of many kinds of cancer cells such as leukemia, lymphatic cancer and other systemic cancer, And the tumors that have eroded the surrounding tissue can't be operated on, and chemotherapy is extremely harmful to the body. Many cancer patients not only suffer from the pain of the tumor itself, but also from the damage caused by chemotherapy drugs, so, It is a common problem for researchers in the world to find anti-tumor drugs with high activity and low toxicity. In this paper, we found that resveratrol extracted from plants has antibacterial, anti-inflammatory, anti-tumor and other biological activities, but the structure contains three phenolic hydroxyl structure, resulting in its own stability and low activity. Therefore, resveratrol was used as a lead compound to methylate hydroxyl in its structure, and cyanide structure was introduced to synthesize some 2-diarylacrylonitrile compounds. The antitumor activity of these compounds was tested by MTT method in vitro. According to the literature, the heterocyclic structure of nitrogen-containing heterocycles is a kind of heterocyclic which is easy to bind to organism, among which 1 ~ (2 +) ~ (2 +) -4-triazole is a recognized important active group, and thiazolones are also a kind of antitumor active group. Therefore, a series of triazolyl thiazolone derivatives were synthesized as bridging bonds, and their antitumor activities were tested by biological activity test. The structures of all compounds were confirmed by 1H NMR and 13C NMR-IR. The results showed that the diarylacrylonitrile compounds had good antitumor activity. Acrylonitrile and 4p in HeLa have stronger antitumor activity than paclitaxel, and have lower toxicity in normal cells, and the antitumor activity of compound 4d is stronger than that of paclitaxel, and the antitumor activity of acrylonitrile is higher than that of paclitaxel, and the antitumor activity of acrylonitrile is higher than that of paclitaxel, and the antitumor activity of acrylonitrile and 4p is stronger than that of paclitaxel in HeLa, and the antitumor activity of acrylonitrile is higher than that of taxol. It shows good selective anticancer effect. These compounds can inhibit the migration of tumor cells and can effectively inhibit the cells staying in G _ 2 / M phase. Triazothiazolone derivatives also showed different levels of antitumor activity, of which 5k [ZAZ-5-N 3-acetyl chylidene-2-butazolyl 3-pyridyl] thiazolyl [32-b] [1-2-4] triazolium-6-triazolium-5-1-one was the most active, and the activity of 5 k [ZH- 5-5-oxy-3-oxy-2-pyridyl] thiazolyl was the best The IC50 in AGS cells was 20.3 卤8.3 渭 M. it was an effective antitumor drug.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R914;R96
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本文编号：2008876