1-(甲基磺醯基)-1,2,3,4-四氫喹啉-7-胺衍生物作為對三陰性乳腺癌細胞的新型抗癌藥物: 設計，合成和活性關係研究

Design, Synthesis, and Structure Activity Relationship Studies of 1-(Methylsulfonyl)-1,2,3,4-tetrahydroquinolin-7-amine Derivatives as a New Class of Anticancer Agent against Triple Negative Breast Cancer Cells

劉譿嬅(HUI-HUA LIU)

指導教授 ： 李文山

國立中正大學/理學院/化學暨生物化學系/碩士(2016年)

摘要

多年來，癌症已位居十大死因之首，乳癌對於女性也是不容小覷，隨著科技的進步，乳癌不在是單一疾病，根據2011年St. Gallen國際乳癌治療準則可將乳癌約分為四種亞型，其中一種亞型為三陰性乳癌，復發及轉移率偏高，且有高比例的抗藥性，降低治療效果，提高死亡率，目前也缺乏標靶。
高速藥物篩選系統(High throughput screening, HTS)是開發藥物的方法之一，相較於傳統藥物開發節省許多時間和費用。
本文是利用高速藥物篩選技術針對三陰性乳癌細胞MDA-MB-231篩選出來的活性化合物(hit compound)，化合物JE01和JE02，進行細胞存活率測試，發現不同培養液會有差異懸殊的活性，接著以化合物JE01和JE02為起源去做一系列的結構修飾，成功合成出化合物JE15，在三陰性乳癌細胞MDA-MB-231中有不錯抑制效果，IC50 = 3.91 μM (DMEM)，IC50 = 1.72 μM (L15)。

關鍵字

三陰性乳癌 ； 高速藥物篩選 ； MDA-MB-231細胞

並列摘要

Over the years, cancer becomes the first leading cause top ten of death. For women, breast cancer also should not be underestimated. With advanced technology, breast cancer is not a single disease. According to the St Gallen International Breast Cancer Conference in the year 2011, there are about four subtypes of breast cancer. One subtype is the triple-negative breast cancer (TNBC) involving the high rate of recurrence and metastasis. Especially, TNBC shows the high proportion of drug resistance, reduction of therapeutic effect, increase of mortality, and also a lack of targeted protein/receptor during drug development.
High throughput screening is one of the methods for drug development. It demonstrates the value of time and cost savings compared to that of the traditional drug discovery.
In the thesis, the hit compounds JE01 and JE02 from high throughput screening technology for triple-negative breast cancer cell line MDA-MB-231 were identified and resynthesized recently. For the cell viability test, we observed disparities in cytotoxic activity in different medium. Based on the hit compounds JE01 and JE02, a series of structural aualogs were successfully synthesized and compound JE15 was observed to have the highest anticancer activity. Compound JE15 possesses potent anticancer activity against triple negative breast cancer MDA-MB-231 with IC50 values of IC50 = 3.91 μM (DMEM), IC50 = 1.72 μM (L15) in two different cell culture mediums.

並列關鍵字

triple Negative Breast Cancer ； high throughput screening ； MDA-MB-231 cell

參考文獻

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