2-甲氧基雌二醇16位修饰类似物的合成及其构效关系
Synthesis and structure-activity relationships of 16-modified analogs of 2-methoxyestradiol.
作者信息
Agoston Gregory E, Shah Jamshed H, Lavallee Theresa M, Zhan Xiaoguo, Pribluda Victor S, Treston Anthony M
机构信息
EntreMed, Inc., Discovery Research Department, 9640 Medical Center Drive, Rockville, MD 20850, USA.
出版信息
Bioorg Med Chem. 2007 Dec 15;15(24):7524-37. doi: 10.1016/j.bmc.2007.09.011. Epub 2007 Sep 14.
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.
合成了一系列16位修饰的2-甲氧基雌二醇类似物，并评估了它们对人脐静脉内皮细胞（HUVEC）和MDA-MB-231细胞的抗增殖活性以及结合敏感性。此外，通过测量雌激素依赖性细胞系MCF7在化合物处理后的细胞增殖来评估这些类似物的雌激素活性。观察到随着16位取代基尺寸的增加，抗增殖活性下降。在葡萄糖醛酸化试验中测试的选定类似物与2-甲氧基雌二醇的清除率相似，但在磺酸盐结合试验中的清除率有所提高。
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