| Summary: | 碩士 === 高雄醫學大學 === 醫藥暨應用化學研究所 === 96 === Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are natural products from many kinds of Streptomyces, and exhibited high bioactivities of antibiotics and antitumors in past reports. In the minor groove of DNA,
an aminal bond is formed through nucleophilic attack of the N2 of a guanine base at the electrophilic C11 position of PBD. This mechanism of PBD-DNA adduct inhibit DNA replication and transcription, which interfere with the tumor cell proliferation.
DC-81 is a important member of PBDs, but it’s a pity to present high cytotoxicity. In this discourse, there are some modification in aromatic A-rings and pyrrole C-rings of DC-81 skeleton to reduce cytotoxicity and increase tumor cells selectivity. And design and synthesis of PBD dimers for enhancing DNA-binding activity and developing high potential antitumor alkylation agents.
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