設計與合成尾對尾比咯苯偶氮駢二聚物抗癌試劑

Design and Synthesis of Tail-to-tail Linked Pyrrolo[2,1-c][1,4]benzodiazepine Dimers as Antitumor Agents

辛孟鴻(Meng-Hung Hsin)

指導教授 ： 王志鉦

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2004年)

摘要

比咯偶氮駢(pyrrolo[2, 1-c][1,4]benzodiazepines, PBDs）是由鏈黴菌所產生DNA結合的抗癌抗生素。而單體的PBD與DNA反應以共價鍵形成DNA複合物以達到阻止DNA複製形成抗癌效果。其中苯環上的碳8位置(頭對頭)的PBDs二聚物組合已被證實比PBDs單體更有細胞活性。

於本論文中我們提出合成尾對尾的新方法。以DC-81為單體為新合成路徑，來合成對稱的立體結構二聚物。同時實驗中也嘗試合成不對稱結構的尾接尾二聚體。

關鍵字

抗癌試劑 ； 尾對尾比咯苯偶氮駢二聚物

並列摘要

The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs)(in Figure 1) is a affiliate of potent DNA-binding antitumor antibiotics which are produced by streptomyces species. These biosynthetically derived compounds are inhibiting DNA replication on account of DNA-antibiotic adducts to react covalent bond. The PBD dimers linked at A-C8 / A-C8` (head-to-head) have shown promising cytotoxicity and efficient cross-linking property.

In this thesis we would like to report a new synthesis of tail-to-tail linked PBDs dimers. The natural product DC-81 was chosen as the monomer PBD unit, and an efficient synthetic pathway developed to provide the target dimers in useful quantities and in a stereochemically homogenous form. Meanwhile, we try to synthesize the asymmetric structure of tail-to-tail linked PBD domers in the experiment.

並列關鍵字

Antitumor Agents ； Tail-to-tail Linked PBDs Dimers

參考文獻

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