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

被引：19

作者：

Lewandowska, Marta ^{[1
]}

Ruszkowski, Piotr ^{[2
]}

Baraniak, Dagmara ^{[1
]}

Czarnecka, Anna ^{[1
]}

Kleczewska, Natalia ^{[1
]}

Celewicz, Lech ^{[1
]}

机构：

[1] Adam Mickiewicz Univ, Fac Chem, PL-60780 Poznan, Poland

[2] Poznan Univ Med Sci, Dept Pharmacol, PL-60806 Poznan, Poland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 67卷

关键词：

3; '-Azido-2; 3 '-dideoxy-5-fluorouridine phosphoramidates; Phosphorylation; Cytotoxic activity; Human cancer cell lines: HeLa; KB and MCF-7; NUCLEOSIDE ANALOGS; BIOLOGICAL-ACTIVITY; PYRIMIDINE DEOXYRIBONUCLEOSIDES; ANTIVIRAL ACTIVITY; TRIESTER METHOD; IN-VIVO; 5-FLUORO-2'-DEOXYURIDINE; CELLS; 5-FLUOROURACIL; CYTOTOXICITY;

D O I：

10.1016/j.ejmech.2013.06.047

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：188 / 195

页数：8

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