Cao Sheng, Wang Yibin, Peng Xiaohua
Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee , 3210 North Cramer Street, Milwaukee, Wisconsin 53211, United States.
J Org Chem. 2014 Jan 17;79(2):501-8. doi: 10.1021/jo401901x. Epub 2014 Jan 6.
We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H2O2-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs.
我们评估了芳基硼酸酯的苄基离去基团和核心结构对H2O2诱导形成用于DNA链间交联的双醌甲基化物的影响。这些芳基硼酸酯诱导DNA交联的机制包括生成酚中间体，随后苄基离去基团离去，导致醌甲基化物（QMs）通过烷基化直接交联DNA。QM的形成是DNA交联的速率决定步骤。更好的离去基团（Br）和逐步形成双醌甲基化物提高了链间交联效率。这些发现为设计新型抗癌前药提供了重要指导。
