کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1371546 | 981847 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Computational & experimental evaluation of the structure/activity relationship of β-carbolines as DYRK1A inhibitors
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کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
DYRK1A has been associated with Down’s syndrome and neurodegenerative diseases, therefore it is an important target for novel pharmacological interventions. We combined a ligand-based pharmacophore design with a structure-based protein/ligand docking using the software MOE in order to evaluate the underlying structure/activity relationship. Based on this knowledge we synthesized several novel β-carboline derivatives to validate the theoretical model. Furthermore we identified a modified lead structure as a potent DYRK1A inhibitor (IC50 = 130 nM) with significant selectivity against MAO-A, DYRK2, DYRK3, DYRK4 & CLK2.
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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 20, 15 October 2014, Pages 4854–4860
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 24, Issue 20, 15 October 2014, Pages 4854–4860
نویسندگان
Binia Drung, Christoph Scholz, Valéria A. Barbosa, Azadeh Nazari, Maria H. Sarragiotto, Boris Schmidt,