Synthesis of a prodrug designed to release multiple inhibitors of the epidermal growth factor receptor tyrosine kinase and an alkylating agent: A novel tumor targeting concept

被引:41
作者
Banerjee, R
Rachid, Z
McNamee, J
Jean-Claude, BJ [1 ]
机构
[1] McGill Univ, Royal Victoria Hosp, Ctr Hlth, Div Med Oncol,Dept Med,Canc Drug Res Lab, Montreal, PQ H3A 1A1, Canada
[2] Hlth Canada, Consumer & Clin Radiat Protect Bur, Ottawa, ON, Canada
关键词
D O I
10.1021/jm030423m
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The synthesis of a novel acetoxymethyltriazene designed to be a prodrug of multiple inhibitors of the epidermal growth factor receptor (EGFR) and a methyldiazonium species is described. Studies with each of the expected metabolites demonstrated significant EGFR tyrosine kinase inhibitory activities and the released methyldiazonium was trapped with p-nitrobenzylpyridine. Their ability to damage genomic DNA in whole cells was demonstrated by using the single cell microelectrophoresis (comet) assay. The results suggest that this approach may well represent a novel drug combination strategy involving single molecules masking multiple bioactive agents.
引用
收藏
页码:5546 / 5551
页数:6
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