Fluorescent 7-diethylaminocoumarin pyrrolobenzodiazepine conjugates: Synthesis, DNA interaction, cytotoxicity and differential cellular localization
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- 作者：Geoffrey Wells ; Marie Suggitt ; Marissa Coffils ; Mirza A.H. Baig ; Philip W. Howard ; Paul M. Loadman ; John A. Hartley ; Terence C. Jenkins ; David E. Thurston
- 关键词：Pyrrolobenzodiazepines ; PBDs ; DNA-binding ; DNA sequence-selective ; Fluorescence conjugates ; Nuclear penetration ; Anticancer agents ; Antitumour agents
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 出版时间：15 March 2008
- 年：2008
- 卷：18
- 期：6
- 页码：2147-2151
- 全文大小：206 K
文摘
The pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) are a class of DNA minor groove binding agents that react covalently with guanine bases, preferably at Pu-G-Pu sites. A series of three fluorescent PBD–coumarin conjugates with different linker architectures has been synthesized to probe correlations between DNA binding affinity, cellular localization and cytotoxicity. The results show that the linker structure plays a critical role for all three parameters.