- 學位論文
斑螫素類似物的合成及其抗癌活性
Synthesis of anhydride modified cantharidin analogues and their anticancer activity
摘要
壹、斑螫素類似物的合成及其抗癌活性 從南方大斑螫 (Mylabris phalerata Pallas) 所分離出的斑螫素(cantharidin) 具有抗癌的作用，特別是原發性肝癌及血癌。由於斑螫素對於腎臟、泌尿道有強烈刺激性，使得其在臨床上應用受到限制。為了改善斑螫素的毒性，以cyclic acid anhydride為起始物和一級胺類進行反應，利用加熱迴流法製備5-phthalimidopyrimidine-2,4 (1H, 3H) -dione及溶熱法製備5-(5-methyl-thiazol-2-ylimino)-4-oxa-tricyclo [5.2.2.02,6] undec-8-en-3-one。 除了上述合成的兩種化合物外，我們另外購買四種化合物(5-aminouracil，6-aminouracil，Endo-5-norbornene-2,3-dicarboxylic anhydride，4-4'-oxydiphthalic anhydride)，將此六種化合物分別對SK-Hep1、Hep G2肝癌細胞株和對大白鼠初代肝細胞來進行體外細胞毒性試驗，接著再以DAPI stain assay證實SK-Hep1、Hep G2肝癌細胞株的死亡是走細胞凋亡 (apoptosis) 的路線。 貳、以維他命 C 及溶熱法合成及鑑定包裹奈米鈰顆粒的碳球 本實驗是以溶熱法在溫度160 - 180 ℃下來製備碳球 (carbon spheres)。本實驗主要以維他命C為碳元素之來源與Ce金屬錯合物反應來製備碳球，以SEM、XRD、FT-IR、1H NMR來鑑定分析所得的碳球。 根據SEM分析顯示：所製備的碳球皆為球狀，且每個碳球之間為同質性的、分散得很均勻。根據粉末XRD分析顯示：以維他命C為碳源的反應中，以異丙醇當溶劑，所製備的碳球其內部能夠包覆Ce金屬奈米顆粒；根據FT-IR分析顯示：包覆有Ce金屬奈米顆粒的碳球表面具有–OH、C=C、C=O官能基；根據1H NMR分析顯示：包覆有Ce金屬奈米顆粒的碳球表面也具有維他命C之-CH2OH官能基。
並列摘要
壹、斑螫素類似物的合成及其抗癌活性 Cantharidin isolated from Mylabris phalerata Pallas and other insects is used traditionally as an anticancer drug especially on hepato- cellular carcinoma and leukaemia. But the highly renel toxicity of cantharidin limits its use.In order to improve the toxicity of cantharidin, we use cyclic acid anhydride and primary amines to synthesize 5-Phth- alimidopyrimidine-2,4 (1H, 3H)-dione by reflux method and 5-(5-methyl- thiazol-2-ylimino)-4-oxa-tricyclo [5.2.2.02,6]undec-8- en-3-one by solv- enthermal method. Except for the two synthesied compounds , we bought another four compounds (5-aminouracil, 6-aminouracil, Endo-5-norbornene-2,3-dicar- boxylic anhydride, 4-4'-oxydiphthalic anhydride). Moreover, we use MTT assay and DAPI stain assay to evaluate the cytotoxicity and cell apoptosis of these compounds on SK-Hep1 and Hep G2 and rat heaptocyte. 貳、以維他命 C 及溶熱法合成及鑑定包裹奈米鈰顆粒的碳球 We synthesized the carbon spheres by using hydrothermal (solvent- hermal) method at 160 - 180 ℃. In the experiment, we useVitamin C as carbon sources to react with Ce metal complex. The resulting products were characterized by using scanning electron microscopy (SEM) , X-ray powder diffractometer (XRD) , FT-IR spectrum analysis (FT-IR) and NMR analysis. The SEM results showed that the carbon spheres are in perfect sph- erical morphology and dispersed uniform.The powder XRD results showed that we use vitamin C as carbon sources in solventhermal condition to synthesize carbon spheres can encapsulate Ce metal nanopa- rticles. The FT-IR results showed that the carbon spheres encapsulate Ce metal nanoparticles possess specially functional group, including –OH, C=C, C=O. The 1H NMR results showed that the carbon spheres encapsulate Ce metal nanoparticles possess -CH2OH functional group from vitamin C.