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

共 50 条

[1] SYNTHESIS AND BIOLOGICAL-ACTIVITIES OF 5'-AZIDO-2',5'-DIDEOXY-5-FLUORO- AND 5'-AMINO-2',5'-DIDEOXY-5-FLUOROURIDINE
LIN, TS
PRUSOFF, WH
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1975, 170 (AUG24): : 54 - 54
[2] FACILE SYNTHESIS OF 2',5'-DIDEOXY-5-FLUOROURIDINE BY THYMIDINE PHOSPHORYLASE
CHAE, WG
CAUCHON, NS
KOZLOWSKI, JF
CHANG, CJ
JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (03): : 1002 - 1005
[3] 3'-AZIDO-2',3'-DIDEOXY-5-HYDROXYMETHYL-URIDINE
LI, J
KUMAR, SVP
STUART, AL
TOURIGNY, G
DELBAERE, LTJ
GUPTA, SV
ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS, 1994, 50 : 1626 - 1629
[4] ANTIRETROVIRAL ACTIVITY, BIOCHEMISTRY, AND PHARMACOKINETICS OF 3'-AZIDO-2',3'-DIDEOXY-5-METHYLCYTIDINE
SCHINAZI, RF
CHU, CK
ERIKSSON, BF
SOMMADOSSI, JP
DOSHI, KJ
BOUDINOT, FD
OSWALD, B
MCCLURE, HM
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1990, 616 : 385 - 397
[5] Pharmacokinetics of 3 '-azido-2 ',3 '-dideoxy-5-methylcytidine in rats
Boudinot, F. D.
Ibrahim, S. S.
Qin, Y.
Chu, C. K.
Schinazi, R. F.
ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1990, 1 (06): : 367 - 371
[6] METABOLISM AND MODE OF SELECTIVE-INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS REPLICATION BY 3'-AZIDO-2',3'-DIDEOXY-5-IODOURIDINE AND 3'-AZIDO-2',3'-DIDEOXY-5-BROMOURIDINE
AUGUST, EM
QIAN, HY
BIRKS, EM
THOMBRE, UA
LIN, TS
PRUSOFF, WH
BIOCHEMICAL PHARMACOLOGY, 1993, 45 (01) : 223 - 230
[7] Synthesis and antiviral activity of 2′-"up"-azido-2′,3′-dideoxy-4′-thionucleosides.
Jeong, LS
Park, YH
Kim, HO
Chun, MW
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2001, 221 : U50 - U50
[8] ANALOGS OF NUCLEOSIDES .16. 5'-HALOGENO-2',3'-SULFITES IN THE SYNTHESIS OF 2',5'-DIDEOXY-5-FLUOROURIDINE AND RELATED ANALOGS
HREBABECKY, H
BERANEK, J
COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 1978, 43 (12) : 3268 - 3278
[9] SYNTHESIS OF 2',3'-DIDEOXYNUCLEOSIDES AND 3'-AZIDO-2',3'-DIDEOXY PYRIDAZINE NUCLEOSIDES AS POTENTIAL ANTIVIRAL AGENTS
RASHWAM, H
KASNAR, B
WISE, DS
DRACH, JC
KUCERA, L
TOWNSEND, LB
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 1992, 204 : 140 - MEDI
[10] SYNTHESIS OF 3'-AZIDO-2',3'-DIDEOXY-BETA-D-ARABINO-HEXOPYRANOSYL NUCLEOSIDES
HANSEN, P
LAU, J
PEDERSEN, EB
NIELSEN, CM
LIEBIGS ANNALEN DER CHEMIE, 1990, (11): : 1079 - 1082

← 1 2 3 4 5 →