کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2029569 1070630 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibition of estrone sulfatase by aromatase inhibitor-based estrogen 3-sulfamates
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Inhibition of estrone sulfatase by aromatase inhibitor-based estrogen 3-sulfamates
چکیده انگلیسی

Our rationale is based on the finding that estrone 3-sulfamate (EMATE, 2d), a typical estrone sulfatase (ES) inhibitor, can be hydrolyzed and the pharmacological effect of the free estrogen contributes to the bioactivity of the sulfamate. A number of 3-sulfamoylated derivatives of the good aromatase inhibitors, 2- and 4-halogeno (F, Cl, and Br) estrones and their estradiol analogs as well as 6β-methyl and phenyl estrones, were synthesized and evaluated as inhibitors of ES in human placental microsomes in comparison with the lead compound EMATE. Among them, 2-chloro- and 2-bromoestrone 3-sulfamates (2b and 2c), along with their estradiol analogs 3b and 3c, were powerful competitive inhibitors with Ki's ranging between 4.0 and 11.3 nM (Ki for EMATE, 73 nM). These four sulfamates as well as the 2-fluoro analogs 2a and 3a inactivated ES in a time-dependent manner more efficiently than EMATE, and 2-halogeno estrone sulfamates 2 also caused a concentration-dependent loss of ES activity. The results may be useful for developing a new class of drugs having a dual function, ES inhibition and aromatase inhibition, for the treatment of breast cancer.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Steroids - Volume 71, Issue 5, May 2006, Pages 371–379
نویسندگان
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