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    Please use this identifier to cite or link to this item: http://ir.cnu.edu.tw/handle/310902800/31987

    標題: 設計合成喜樹鹼前驅藥物
    Design and Synthesis of Piperazine 10-Hydroxycamptothecin Glucuronide Prodrug
    作者: 陳國輝
    貢獻者: 藥學系
    關鍵字: 喜樹鹼
    日期: 2018
    上傳時間: 2019-02-27 16:51:03 (UTC+8)
    摘要: 喜樹鹼具有良好的抗癌效果,但其水溶性極差,為了增加水溶解度,並讓藥物有對腫瘤專一性,先期本實驗室設計合成喜樹鹼葡萄醣醛酸前驅藥(9-ACG和10-HCG),前驅藥只在腫瘤附近被葡萄醣醛酸酶活化達到標靶作用。據研究顯示,10-HCG對於葡萄醣醛酸酶有較好親和性,但是水溶性卻沒有9-ACG好,因此設計在10-HCG的中間體添加水溶性基團N-methylpiperazine,合成目標物10-HCPG,具有更好的親水性,降低細胞毒性,保留酵素親和力,並對腫瘤有專一性。在合成10-HCPG時,中間體會因為立體障礙,而無法順利與喜樹鹼鍵結,降低產率,本研究為了解決此問題,中間體會先鍵結立體障礙較小的2-amino-5-hydroxybenzaldehyde再與tricyclic ketone縮合,以提高合成產率。
    Camptothecin has good anti-cancer activity but have poor water solubility. For improving water solubility, our laboratory designed and synthesized two glucuronide prodrugs of Camptothecin (9-ACG and 10-HCG) which will mainly be activated at tumor site expressing large number of β-glucuronidase. According to previous studies, 10-HCG have good affinity for β-glucuronidase but water solubility is not better than 9-ACG. Therefore, we design and synthesize the target compound 10-HCPG by creating N-methyl piperazine on the spacer of 10-HCG, expect for good water solubility, stable in blood, low cytotoxicity, good affinity with β-glucuronidase and specific to tumor cells. Synthesis of 10-HCPG have a problem which spacer conjugating with 10-hydroxycamptothecin have steric effect. For solving this problem, spacer conjugate with 2-amino-5-hydroxybenzaldehyde which have less steric effect and conjugate with tricyclic ketone with condensation reaction
    Appears in Collections:[藥學系(所)] 博碩士論文

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