Synthesis and evaluation of taxol-folic acid conjugates as targeted antineoplastics

被引：99

作者：

Lee, JW ^{[1
]}

Lu, JY ^{[1
]}

Low, PS ^{[1
]}

Fuchs, PL ^{[1
]}

机构：

[1] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 07期

关键词：

D O I：

10.1016/S0968-0896(02)00019-6

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of Taxol derivatives tethered at C2' and C-7 to glutamate and folate have been synthesized for evaluation as prodrugs which release Taxol via hydrolytic lability of their alpha-alkoxy and alpha-amino esters. The half-time for hydrolysis of these materials was determined in pH 7 and pH 5 buffer. The in vitro cytotoxicity has been assessed in cell culture against A-549 lung cancer, MCF-7 breast cancer, and HT-29 colon cancer. Selected agents were further screened for folate binding and competitive binding with free folic acid, One agent (54), further evaluated in animal Studies as found to increase the lifespan in mice, but was less effective than Taxol itself. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：2397 / 2414

页数：18

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