本文選題：白藜蘆醇 + 2�。� 參考：《延邊大學(xué)》2017年碩士論文

【摘要】：癌癥是威脅人類健康的一種惡性疾病,僅在中國,每年就有200萬人因癌癥死去,目前根治癌癥的方式為手術(shù)治療,但由于許多種腫瘤細(xì)胞如白血病,淋巴癌等全身性癌癥、以及已經(jīng)侵蝕周圍組織的腫瘤無法進(jìn)行手術(shù),而化療對(duì)身體危害極大,許多腫瘤患者不僅要承受腫瘤本身的疼痛,而且要承受化療藥物對(duì)身體造成的傷害,所以,尋找到活性高毒性小的抗腫瘤藥物是世界學(xué)者面臨的共同難題。本論文通過查閱資料,發(fā)現(xiàn)從植物中提取的白藜蘆醇具有抗菌、抗炎、抗腫瘤等多種生物活性,但由于結(jié)構(gòu)中含有三個(gè)酚羥基結(jié)構(gòu),導(dǎo)致其自身穩(wěn)定性較差,并且活性較低,所以將白藜蘆醇作為先導(dǎo)化合物,其結(jié)構(gòu)中的羥基進(jìn)行甲基化,并引入氰基結(jié)構(gòu)合成一些列2,3-二芳基丙烯腈類化合物,所合成的化合物通過MTT等方法檢測(cè)其體外抗腫瘤活性。根據(jù)文獻(xiàn)報(bào)道,含氮雜環(huán)結(jié)構(gòu)是一種易與生物體結(jié)合的雜環(huán),其中1,2,4-三氮唑?yàn)橐环N公認(rèn)的重要活性基團(tuán),同時(shí),噻唑酮類化合物也是一種抗腫瘤活性基團(tuán),所以將兩者進(jìn)行拼合,作為橋連鍵,合成一系列三唑并噻唑酮類衍生物,并通過生物活性的測(cè)試,檢測(cè)其抗腫瘤活性。所有化合物經(jīng)~1HNMR和~(13)C NMR,IR等進(jìn)行結(jié)構(gòu)確證。結(jié)果顯示,2,3-二芳基丙烯腈類化合物具有較好的抗腫瘤活性,其中,化合物4d[(Z)-2-(3,5-二甲氧基苯基)-3-(4-溴基苯基)]丙烯腈與4p[(Z)-2-(3,5-二甲氧基苯基)-3-(乙氧基苯基)丙烯腈)]在HeLa中的抗腫瘤活性強(qiáng)于紫杉醇,而且在正常細(xì)胞中有較低的毒性,表現(xiàn)出很好的選擇性抗癌作用。該類化合物能夠抑制腫瘤細(xì)胞的遷移作用,并能有效的抑制細(xì)胞停留在G2/M期。三唑并噻唑酮類衍生物也表現(xiàn)出不同程度的抗腫瘤活性,其中5k[(Z)-5-(3-乙酰氧基基亞芐基)-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細(xì)胞中的IC50值為20.3±8.3μM,是一種有效的抗腫瘤藥物。
[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 鹵8.3 渭 M. it was an effective antitumor drug.
【學(xué)位授予單位】：延邊大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R914;R96
，

本文編號(hào)：2008876