評估維生素E衍生物抗光老化效果及對皮膚癌細胞抗癌效果研究探討

The Evaluation of the Anti-photoaging Effects of the α-Tocopherol Analogs and Anticancer Effects in Human Skin Cancer Cells

沈明羽(Ming-Yu Shen)

指導教授 ： 顏金鳳

共同指導教授 ： 楊世群(Shyh-Chyun Yang)

高雄醫學大學/藥學院/藥學研究所/碩士(2010年)

https://doi.org/10.6832/KMU.2010.00038

摘要

中文摘要

近期研究指出vitamin E衍生物vitamin E succinate (α-VES)或稱α-tocopheryl succinate和α-tocopheryloxyacetic acid (α-TEA) (1)具有proapoptotic效果。本論文研究目的為合成其他vitamin E衍生物(1~19)並評估半合成衍生物的抗氧化效果和對人類皮膚癌細胞抗癌效果的研究探討。
本研究合成了19個化合物，α-tocopheryloxyacetic acid (α-TEA) (1)、α-tocopheryl-3,3-dimethyl glutarate (2)、α-tocopheryl-2,2-dimethyl glutarate (3)、α-tocopheryl glutarate (4)、α-tocopheryl-3-methyl glutarate (5)、3-α-tocopheryl-N,N-diethylpropanamine (6)、3-α-tocopheryl-N-tert-butylpropanamine (7)、3-α-tocopheryl-N-sec-butylpropanamine (8)、3-α-tocopheryl-N-propylpropanamine (9)、3-α-tocopheryl-N-cyclohexanylpropanamine (10)、N-(3-α-tocopherylpropyl)piperidine (11)、α-tocopheryl crotonate (12)、α-tocopheryl propionate (13)、α-tocopheryl isobutyrate (14)、α-tocopheryl butyrate (15)、α-tocopheryl isovalerate (16)、α-tocopheryl palmitate (17)、α-tocopheryl p-toluenesulfonate (18)和N,N-diethyl-2-α-tocopheryloxyacetamide (19)，並進行半合成衍生物的抗氧化和對人類皮膚癌細胞抗癌效果的研究探討。
合成的vitamin E衍生物利用MTT assay進行對melanoma和basal cell 癌細胞存活率評估，實驗結果顯示??-VES在3 mM和10 mM濃度下明顯減少了melanoma和basal cell癌細胞存活率。在抗氧化實驗結果顯示，化合物9對於ABTS的抑制具有最好效果，本論文將進一步探討半合成衍生物的構造及活性之間的相關性。

關鍵字

維生素E ； 抗氧化 ； 抗皮膚癌

並列摘要

ABSTRACT

Recent results showed that vitamin E derivatives, vitamin E succinate (α-VES) or α-tocopheryl succinate and α-tocopheryloxyacetic acid (α-TEA) (1) are proapoptotic agents. Our research goal is to synthesize others vitamin E derivatives (1~19) and evaluate their antioxidant effects and the anticancer effects in human skin cancer cells.
19 compounds have been synthesized, α-tocopheryloxyacetic acid (α-TEA) (1), α-tocopheryl-3,3-dimethyl glutarate (2), α-tocopheryl-2,2-dimethyl glutarate (3), α-tocopheryl glutarate (4), α-tocopheryl-3-methyl glutarate (5), 3-α-tocopheryl-N,N-diethylpropanamine (6), 3-α-tocopheryl-N-tert-butylpropanamine (7), 3-α-tocopheryl-N-sec-butylpropanamine (8), 3-α-tocopheryl-N-propylpropanamine (9), 3-α-tocopheryl-N-cyclohexanylpropanamine (10), N-(3-α-tocopherylpropyl)piperidine (11), α-tocopheryl crotonate (12), α-tocopheryl propionate (13), α-tocopheryl isobutyrate (14), α-tocopheryl butyrate (15), α-tocopheryl isovalerate (16), α-tocopheryl palmitate (17), α-tocopheryl p-toluenesulfonate (18) and N,N-diethyl-2-α-tocopheryloxyacetamide (19) and evaluate their antioxidant effects and anticancer effects in human skin cancer cells.
The cell viability of melanoma and basal cell carcinoma cells test was determined by MTT assay. The results showed that a hydrolyzable ester derivative (α-VES) significantly decreased the cell viability of melanoma and basal cell carcinoma cells at concentrations of 3 mM and 10 mM respectively. In the antioxidant effects, compound 9 showed the most potent ABTS inhibition effect. The structure-activity-relationship of the semisynthetic derivatives will be discussed.

並列關鍵字

vitamin E ； tocopherol ； VES ； TEA

參考文獻

參考文獻

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2. Schwarz, K. (1965) Role of vitamin E, selenium, and related factor in experimental nutritional liver disease. Federation Proc. 24, 58-67.

3. Tappel, A. L. (1962) Vitamin E as the biological lipid antioxidant. Vitam. Horm. 20, 493–510.

4. IUPAC-IUB Joint Commission on Biochemical Nomenclature. (1982) Nomenclature of tocoperols and related compounds, Recommendations 1981. Pure & Appl. Chem. 54, 1507-1510.