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Published on: August 28, 2019
Synthesis and structure-activity relationships of 16-modified analogs of 2-methoxyestradiol
Gregory E Agoston1, Jamshed H Shah, Theresa M Lavallee
1EntreMed, Inc., Discovery Research Department, 9640 Medical Center Drive, Rockville, MD 20850, USA.
Abstract:
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.
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