Troxacitabine prodrugs for pancreatic cancer

A. D. Adema, M. Radi, J. Daft, J. Narayanasamy, E. K. Hoebe, L. E. Alexander, C. K. Chu, G. J. Peters

Research output: Contribution to journalArticle*Academicpeer-review

Abstract

Troxacitabine is a cytotoxic deoxycytidine analogue with an unnatural L-configuration, which is activated by deoxycytidine kinase (dCK). The configuration is responsible for differences in the uptake and metabolism of troxacitabine compared to other deoxynucleoside analogues. The main drawback in the use of most nucleoside anticancer agents originates from their hydrophilic nature, which property requires a high and frequent dosage for an intravenous administration. To overcome this problem several troxacitabine prodrugs modified in the aminogroup with a linear aliphatic chain with a higher lipophilicity were developed. To determine whether these prodrugs have an advantage over Troxacitabine pancreatic cancer cell lines were exposed to Troxacitabine and the lipophilic prodrugs. The addition of linear aliphatic chains to troxacitabine increased sensitivity of pancreatic cancer cell lines to the drug > 100-fold, possibly due to a better uptake and retention of the drug
Original languageEnglish
Pages (from-to)1073-1077
JournalNucleosides, nucleotides & nucleic acids
Volume26
Issue number8-9
DOIs
Publication statusPublished - 2007

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