کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1356651 981144 2008 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis, structure–activity relationships and molecular modeling studies of new indole inhibitors of monoamine oxidases A and B
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis, structure–activity relationships and molecular modeling studies of new indole inhibitors of monoamine oxidases A and B
چکیده انگلیسی

New monoamine oxidase inhibitors were synthesized as indole analogues of a previously reported pyrrole series. Several compounds were potent MAO-A (12, 17, 19–22, 31, 36, and 37) or MAO-B (14, 20, 24, 38, 44, and 46) inhibitors, and had Ki values in the nanomolar concentration range. In particular, 22 (Ki = 0.00092 μM, and SI = 68,478) was exceptionally potent and selective as MAO-A inhibitor. In molecular modeling studies, compounds 22, 24, 44, and 46 positioned the indole ring into an aromatic cavity of MAO-A, and established π–π stacking interactions with Tyr407, Tyr444, and FAD cofactor. However, only compound 22 was able to form hydrogen bonds with FAD, a finding which was in accordance with its potent anti-MAO-A activity. Conversely, 22/MAOB complex was highly unstable during the MD simulation.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 22, 15 November 2008, Pages 9729–9740
نویسندگان
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