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

• Phosphoramidates of 3′-azido-2′,3′-dideoxy-5-fluorouridine were synthesized.
• Obtained phosphoramidates were evaluated for their cytotoxic activity.
• The highest activity was displayed by phosphoramidate with the N-ethyl substituent.
• Phosphoramidate with N-propargyl substituent exhibited also fairly high activity.

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.

A series of 4-chlorophenyloxy N-alkyl phosphoramidates of 3′-azido-2′,3′-dideoxy-5-fluorouridine were synthesized and evaluated for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7).Figure optionsDownload as PowerPoint slide