Synthesis and structure-activity relationships of 16-modified analogs of 2-methoxyestradiol.
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.
Agoston
Gregory E
GE
EntreMed, Inc., Discovery Research Department, 9640 Medical Center Drive, Rockville, MD 20850, USA.
Shah
Jamshed H
JH
Lavallee
Theresa M
TM
Zhan
Xiaoguo
X
Pribluda
Victor S
VS
Treston
Anthony M
AM
D000077584:2-Methoxyestradiol; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002277:Carcinoma / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004958:Estradiol; D000077584:2-Methoxyestradiol