Synthesis and structure-activity relationships of 16-modified analogs of 2-methoxyestradiol

被引：21
|
作者：
Agoston, Gregory E. [1 ]
Shah, Jamshed H. [1 ]
LaVallee, Theresa M. [1 ]
Zhan, Xiaoguo [1 ]
Pribluda, Victor S. [1 ]
Treston, Anthony M. [1 ]
机构：
[1] EntreMed Inc, Discovery Res Dept, Rockville, MD 20850 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 24期
关键词：
2-methoxyestradiol analogs; structure-activity relationships; antiproliferative agent; conjugation;
D O I：
10.1016/j.bmc.2007.09.011
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 16-modified 2-methoxyestradiol analogs were synthesized and evaluated for antiproliferative activity toward HUVEC and MDA-MB-231 cells, and for susceptibility to conjugation. In addition, the estrogenicity of these analogs was accessed by measuring cell proliferation of the estrogen-dependent cell line MCF7 in response to compound treatment. It was observed that antiproliferative activity dropped as the size of the 16 substituent increased. Selected analogs tested in glucuronidation assays had similar rates of clearance to 2-methoxyestradiol, but had enhanced clearance in sulfonate conjugation assays. (c) 2007 Elsevier Ltd. All rights reserved.
引用
收藏
页码：7524 / 7537
页数：14
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