Synthesis and biological evaluation of novel conjugates of podophyllotoxin and 5-FU as antineoplastic agents

被引：51

作者：

Chen, Shi-Wu ^{[1
,2
]}

Xiang, Rong ^{[1
,3
]}

Liu, Jian ^{[2
]}

Tian, Xuan ^{[2
]}

机构：

[1] Lanzhou Univ, Sch Pharm, Lanzhou 730000, Peoples R China

[2] Lanzhou Univ, Sates Key Lab Appl Organ Chem, Lanzhou 730000, Peoples R China

[3] Lanzhou Hosp Tradit Chinese Med Traumatocomium, Lanzhou 730000, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 08期

关键词：

Podophyllotoxin; 5-FU; Antineoplastic agents; Calf thymus DNA; DNA TOPOISOMERASE-II; ANTITUMOR AGENTS; ANTICANCER DRUGS; DERIVATIVES; INHIBITORS; 4'-DEMETHYLEPIPODOPHYLLOTOXIN; CHEMOTHERAPY; ANALOGS; CANCER; DESIGN;

D O I：

10.1016/j.bmc.2009.03.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

A series of novel conjugates of podophyllotoxin and 5-FU were designed using association strategy and were synthesized by coupling 4'-demethylepipodophyllotoxin with 5-FU-N(1)-alkyl amino acid ester. These derivatives have been evaluated for cytotoxicity in vitro against tumour cell lines (HL-60, K562, A-549 and AGS), and their octanol-water partition coefficients (logP) were also determined. As compared with VP-16, most compounds showed superior water solubility, as well as more potent inhibitions against these four tumour cell lines. Compound 21 showed interaction with calf thymus DNA, and it was relatively resistant to metabolism by human plasma. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：3111 / 3117

页数：7

共 27 条

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