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
- 7 November 2003
- journal article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 46 (25) , 5546-5551
- https://doi.org/10.1021/jm030423m
Abstract
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.Keywords
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