Synthesis and biological activity of a gemcitabine phosphoramidate prodrug |
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Authors: | Wu Weidong Sigmond Jennifer Peters Godefridus J Borch Richard F |
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Affiliation: | Department of Medicinal Chemistry and Molecular Pharmacology and Cancer Center, Purdue University, West Lafayette, Indiana 47907, USA. |
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Abstract: | A gemcitabine (2',2'-difluorodeoxycytidine, dFdC) phosphoramidate prodrug designed for the intracellular delivery of gemcitabine 5'-monophosphate was synthesized. The prodrug was about an order of magnitude less active than gemcitabine against wild-type cells, and the nucleoside transport inhibitor dipyridamole reduced prodrug activity. The prodrug was more active than gemcitabine against two deoxycytidine kinase-deficient cell lines. The results suggest that the prodrug is a potent growth inhibitor that can bypass dCK deficiency at higher drug concentrations. |
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