Design and Synthesis of Pyrrolo[2,1-c][1,4]benzodiazepine Hybrids agent and Dimers as Antitumor Alkylation Agents

• Main Authors: Chung-Yu Chen, 陳建宇
• Other Authors: Jeh-Jeng Wang
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/cgavpj

碩士 === 高雄醫學大學 === 醫藥暨應用化學研究所 === 97 === Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are natural products extracted from many kinds of Streptomyces, and exhibited high bioactivities of anti-biotics and anti-tumors in past reports.The PBDs can be interact with DNA in high sequence – selective active, because PBDs can form a covalent bond with DNA guanine in the minor groove. This mechanism of PBDs-DNA adduct inhibit DNA replication and transcription, which interfere with the tumor cell proliferation. This adduct formation is thought to lead to the observed biological activity. In this thesis, we designed and syntheized a series of Gallic Acid derivatives linked with PBDs as anti-tumor agents. As well as synthesized a PBDs dimmer which cross-linking with ρ-xylylene bromide at head to head(C-8/A). Four of them has been synthesized and sent to NCI for screening test. This hybrid agent compounds had great biological activity result.