Article ID Journal Published Year Pages File Type
1392647 European Journal of Medicinal Chemistry 2013 8 Pages PDF
Abstract

•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.

Graphical abstractA 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 full-size imageDownload as PowerPoint slide

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Physical Sciences and Engineering Chemistry Organic Chemistry
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