含碘白杨素衍生物的合成及其抗甲状腺癌活性的研究

发布时间：2018-06-30 07:32

本文选题：甲状腺癌 + 含碘白杨素衍生物　；参考：《南华大学》2016年硕士论文

【摘要】：近年来,我国甲状腺癌的发病率逐年提高。临床上使用的抗甲状腺癌药物,由于肿瘤细胞的耐药和一系列不良反应从而限制了的它们应用。因此,通过不同途径寻找高效低毒的抗甲状腺癌药迫在眉睫。以天然化合物的活性成分为先导化合物,进行结构修饰,合成生物活性强、生物利用率高、毒性较低的抗甲状腺癌药已经成为当今新药研制的热点。白杨素作为一种天然的黄酮类化合物,在体外对甲状腺癌等多种癌细胞有效,但因其生物利用度低,限制了在临床上的应用。碘是合成甲状腺激素所必需的原料,而甲状腺激素跟甲状腺癌的发生又密不可分。因此,课题组考虑将碘元素引入白杨素中,合成一系列的含碘白杨素衍生物,研究其抗甲状腺癌的活性。本论文主要分为以下两部分:第一部分:含碘白杨素衍生物的合成。通过Houben-Hoesch反应、羟醛缩合和酸化环合、烷基化等一系列的反应,以间苯二酚为原料合成了18个新的的含碘白杨素衍生物。第二部分:以5-氟尿嘧啶为对照品,通过MTT法测试了含碘白杨素衍生物对甲状腺癌细胞的抑制增殖(SW-579和TT)作用。结果表明:含碘白杨素衍生物对甲状腺癌细胞的抑制增殖作用强于5-氟尿嘧啶。特别是化合物10抑制TT细胞株增殖的IC50值为6.268μM远低于5-氟尿嘧啶IC50值18.411μM。化合物21抑制SW-579细胞株增殖IC50值为3.488μM远低于5-氟尿嘧啶IC50值59.391μΜ。
[Abstract]:In recent years, the incidence of thyroid cancer in China has increased year by year. Clinical use of anti-thyroid cancer drugs, due to tumor cell resistance and a series of adverse reactions limit their use. Therefore, it is urgent to find effective and low toxic anti-thyroid cancer drugs through different ways. With the active components of natural compounds as the lead compounds, structural modification, synthesis of high bioactivity, high bioavailability, low toxicity anti-thyroid cancer drugs have become a hot spot in the development of new drugs. As a kind of natural flavonoids, alginine is effective to thyroid carcinoma and other cancer cells in vitro, but its low bioavailability limits its clinical application. Iodine is essential for the synthesis of thyroid hormones, which are closely associated with thyroid carcinogenesis. Therefore, the study group considered introducing iodine element into the white poplar to synthesize a series of iodide-containing salicylidene derivatives to study its anti-thyroid cancer activity. This thesis is divided into the following two parts: the first part: the synthesis of the derivatives containing iodide. A series of reactions such as Houben-Hoesch reaction, hydroxaldehyde condensation and acidizing cyclization and alkylation were used to synthesize 18 new iodine-containing white salicylidene derivatives from resorcinol. The second part: using 5-fluorouracil as the reference substance, the inhibitory effects of iodide-containing alicylin derivatives on the proliferation of thyroid cancer cells (SW-579 and TT) were measured by MTT assay. The results showed that the inhibitory effect of iodized alicylin derivatives on the proliferation of thyroid cancer cells was stronger than that of 5 fluorouracil. In particular, the IC50 of compound 10 was significantly lower than that of 5-fluorouracil (18.411 渭 M) in inhibiting the proliferation of TT cell lines. The IC50 value of compound 21 was significantly lower than that of 5-fluorouracil IC50 (59.391 渭 m) in inhibiting the proliferation of SW-579 cell line.
【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

【相似文献】