Banerjee Ranjita, Rachid Zakaria, McNamee James, Jean-Claude Bertrand J
Department of Medicine, McGill University Health Center/Royal Victoria Hospital, Montreal, H3A 1A1 Quebec, Canada.
J Med Chem. 2003 Dec 4;46(25):5546-51. doi: 10.1021/jm030423m.
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.
本文描述了一种新型乙酰氧基甲基三氮烯的合成，该化合物被设计为表皮生长因子受体（EGFR）多种抑制剂和甲基重氮鎓物种的前药。对每种预期代谢物的研究表明，它们具有显著的EGFR酪氨酸激酶抑制活性，释放的甲基重氮鎓被对硝基苄基吡啶捕获。通过单细胞微电泳（彗星）试验证明了它们在全细胞中破坏基因组DNA的能力。结果表明，这种方法很可能代表了一种涉及单分子掩盖多种生物活性剂的新型药物组合策略。
