Design and Synthesis of Indole LinkedPyrrolo[2,1-c][1,4]benzodiazepineHybrides Anticancer Alkylating Agents

• Main Authors: Chih-Sheng Cheng, 鄭致昇
• Other Authors: Jeh-Jeng Wang
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/02485640249573530724

碩士 === 高雄醫學大學 === 醫藥暨應用化學系碩士班 === 92 === The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) is a family of Anti-cancer agents derived form Streptomyces species. The PBDs can interact with DNA in a sequence－selective fashion，and form a covalent bond with a guanine base in the minor groove of DNA.We have studied hybrid agents based on the DC-81 coupled with indole carboxylate to improve sequence selective of natural PBDs. After testing in vivo and vitro，these hybride agents exhibit cytotoxicity across some kinds of cancer cell lines. The purpose of this thesis is to design and synthesize hybride agents which is formed through the combination of DC-81 and indole carboxylate. Therefore，we designed hybride agents based on the DC-81 coupled with indole carboxylate that contained nitro group on its benzene，to produce a novel anticancer alkylating agent. First，DC-81 was synthesized in the effective route we had reported and then was made synthesis indole carboxylate that contained nitro group on its benzene. Finally，linking Indole carboxylate with C8 position on A ring of DC-81 ，but not creating anti-cancer agents we expected every time.