Synthesis of 3'-azido-2',3'-dideoxy-5-fluorouridine phosphoramidates and evaluation of their anticancer activity

  • Eur J Med Chem. 2013 Sep:67:188-95. doi: 10.1016/j.ejmech.2013.06.047.
Marta Lewandowska  1 ,  Piotr Ruszkowski ,  Dagmara Baraniak ,  Anna Czarnecka ,  Natalia Kleczewska ,  Lech Celewicz
Affiliations
  • 1. Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka St 6, 60-780 Poznań, Poland.
PMID: 23867603 DOI: 10.1016/j.ejmech.2013.06.047
Abstract

A series of novel 4-chlorophenyl N-alkyl phosphoramidates of 3'-azido-2',3'-dideoxy-5-fluorouridine (12-21) were synthesized by means of phosphorylation of 3'-azido-2',3'-dideoxy-5-fluorouridine (4) with 4-chlorophenyl phosphoroditriazolide (10) followed by a reaction with the appropriate amine. The synthesized phosphoramidates (12-21) were evaluated for their cytotoxic activity in three human Cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7) using the sulforhodamine B (SRB) assay. The highest activity in all the investigated Cancer cells was displayed by phosphoramidate 13 with the N-ethyl substituent and its activity was much higher than that of the parent nucleoside. Also phosphoramidate 17 with the N-propargyl substituent exhibited good activity in all the used cell lines.

Keywords
3’-Azido-2′,3′-dideoxy-5-fluorouridine phosphoramidates; Cytotoxic activity; Human cancer cell lines: HeLa, KB and MCF-7; Phosphorylation.