کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2198341 1551009 2006 4 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Benzothiazole derivatives as novel inhibitors of human 11β-hydroxysteroid dehydrogenase type 1
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Benzothiazole derivatives as novel inhibitors of human 11β-hydroxysteroid dehydrogenase type 1
چکیده انگلیسی

Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have considerable potential as treatments for metabolic diseases, such as diabetes mellitus type 2 or obesity. Here, we report the discovery and synthesis of a series of novel benzothiazole derivatives and their inhibitory activities against 11β-HSD1 from human hepatic microsomes measured using a radioimmunoassay (RIA) method. The benzothiazole derivatives 1 and 2 showed greater than 80% inhibition for 11β-HSD1 at 10 μM and exhibited IC50 values in the low micromolar range. The preliminary SAR study suggested the introduction of a chlorine substituent at the 4 position of the benzothiazole ring greatly enhanced the inhibitory activities. Docking studies with the benzothiazole derivative 1 into the crystal structure of human 11β-HSD1 revealed how the molecule may interact with the enzyme and cofactor.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 248, Issues 1–2, 27 March 2006, Pages 214–217
نویسندگان
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