設計及合成含藥物之新穎鉑錯合物; Design and Synthesis of New Drug-Containing Platinum Complexes

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题名:	設計及合成含藥物之新穎鉑錯合物;Design and Synthesis of New Drug-Containing Platinum Complexes
作者:	葉子聖;Tzu-sheng Yeh
贡献者:	化學研究所
关键词:	鉑;藥物;drug;platinum
日期:	2010-07-16
上传时间:	2010-12-08 14:16:51 (UTC+8)
出版者:	國立中央大學
摘要:	於本篇論文中，本人發展一系列具有雙重功效的抗癌前驅藥物之新型有機鉑錯合物的合成路徑。此外，本人亦藉由核磁共振光譜儀(NMR)、傅立葉轉換紅外線光譜儀(FTIR)、紫外光光譜儀(UV)之技術來討論Vorinostat (5)、Acetohydroxamic acid (7)、Bufexamac (9) and Hydroxyurea (12)這些抗癌藥物與鉑金屬之間的鍵結，首先Vorinostat (5)經由實驗及光譜證明是以Hydroxamic acid官能基中的N原子與Sulfoplatin (4)之鉑金屬鍵結，Acetohydroxamic acid (7)、Bufexamac (9)這兩個一樣含有Hydroxamic acid官能基的藥物於更進一步的實驗也被證明是以Hydroxamic acid官能基中的N原子與Sulfoplatin (4)之鉑金屬鍵結，Hydroxyurea (12)和前述Vorinostat (5)、Acetohydroxamic acid (7) and Bufexamac (9)三種藥物一樣具有Hydroxamic acid官能基，但是此藥物卻無法和Sulfoplatin (4)反應，而無法得到我們所預期的產物。最後我們合成出新穎鉑錯合物6, 8, 10且發展出以Hydroxamic acid官能基與鉑金屬鍵結的方法，也確定了其鍵結的形式，此類含Hydroxamic acid官能基的藥物預期於將來會有更多更深入的研究與發展。 A synthetic pathway of novel organoplatinum complex as anti-cancer prodrugs with dual functions was developed. On the other hand, we investigated the binding mod of drugs “Vorinostat (5)、Acetohydroxamic acid (7)、Bufexamac (9) and Hydroxyurea (12)” to platinum metal by NMR(Nuclear magnetic resonance), FTIR(Fourier transform infrared), UV (Ultraviolet) spectroscopy. First the binding mod between Vorinostat (5) and Sulfoplatin (4) was proved by experiments and spectroscopy, Vorinostat (5) binding to Sulfoplatin (4) with nitrogen atom in hydroxamic acid functional group. Acetohydroxamic acid (7) and Bufexamac (9) with hydroxamic acid functional group also show the same binding mod with Sulfoplatin (4) just like Vorinostat (5). Hydroxyurea (12) and the aforementioned drugs “Vorinostat (5), Acetohydroxamic acid (7) and Bufexamac (9)” has the same hydroxamic acid functional group, but it did not work in the same experimental conditions as aforementioned drugs “Vorinostat (5), Acetohydroxamic acid (7) and Bufexamac (9)”, it will be discussed in this contents of my thesis. Furthermore, the platinum complex 6, 8, 10 with hydroxamic acid functional group was expected for more study and investigation in the future.
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