抗癌新藥物－烷硫基秋水仙與胸腺核苷衍生物之合成

The New Anticancer agents-synthesis of Derivatives from Thiocolchicine and Thymidine

廖焜熙(Kun-His Liao)

《致遠管理學院學報》 2_3期 (2007/09) Pp. 15-40

https://doi.org/10.6595/BDCM.2007.2(3).2

摘要

癌症是當今危害人類的大敵，許多研究均在盡心力，以期發現完全治療的藥物。秋水仙素及其許多衍生物，具有強力的抗炎性、抑制細胞有絲分裂及腫瘤生長的作用。但由於水溶性較低，不易進入細胞內發揮作用。胸腺核苷及其許多衍生物，能抑制惡性腫瘤細胞分裂，且其結構上有氫氧基(hydroxyl group)，所以水溶性較高。因此為了增強秋水仙素的水溶性及抗癌性，本研究將秋水仙素及胸腺核苷，兩大系列化合物連接起來，形成一個有利的抗癌新藥物的特性。本研究以此兩化合物為起始物，經許多步驟的合成過程，合成一系列的衍生物(2a, 2b, 3a, 3b, 2A, 3A, 4A)。再藉壬二醯氯(azelaoyl chloride)為中間體，將秋水仙素及胸腺核苷連接。最後合成二個新化合物5a及5b，以提供抗癌藥理試驗。

關鍵字

秋水仙素 ； 胸腺核苷 ； 秋水仙－胸腺核苷衍生物 ； 抗癌藥 ； 壬二醯氯

並列摘要

Cancer is one of the greatest enemies for human beings today, and lots of efforts have been made to find effective cures. Colchicine and a number of its derivatives have been reported to be powerful anti-inflammatories, mitotic poisons and inhibitors of tumor growth. However, it is not easy to enter cells and works because of its low water solubility. Thymidine and many of its derivatives have been known to be able to suppress the malignant tumor cells to split. Furthermore, its water solubility is very high due to the presence of a hydroxyl group in the structure. Based on these facts, the above two series of compounds were joined in this study to form more favorable characteristics to the new anticancer drugs with higher solubility and efficiency. Colchicine and thymidine were used as starting material, through several synthetic courses, to produce a series of derivatives, including 2a, 2b, 3a, 3b, 2A, 3A, and 4A. In the processes, azelaoyl chloride was applied as an intermediate to link colchicine and thymidine together. Finally, two new compounds, 5a and 5b, were successfully synthesized and will be going to proceed pharmacological tests.

並列關鍵字

Colchicine ； Thymidine ； Colchicine-Thymidine Derivative ； Anticancer agent ； Azelaoyl chloride

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