کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8327023 | 1540198 | 2018 | 18 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
New cholinesterase inhibitors for Alzheimer's disease: Structure activity relationship, kinetics and molecular docking studies of 1-butanoyl-3-arylthiourea derivatives
ترجمه فارسی عنوان
مهارکننده های جدید کولین استراز برای بیماری آلزایمر: رابطه فعالیت ساختاری، سینتیک و مطالعات تکاملی مولکولی مشتقات 1-بتائونییل-3-آریلتیورا
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
چکیده انگلیسی
Highly progressive neurodegenerative disorder generally known as Alzheimer's disease (AD), is a type of dementia, which is very common in elderly. The most common symptoms may include loss of memory along with disturbed behavioral and cognitive functions. Until now, only 4 cholinesterase (ChE) inhibitors are approved by FDA for symptomatic treatment of AD. Aroyl thiourea derivatives are well known bioactive organic molecules containing carbonyl and thiocarbonyl functional groups. Here, total 14 different thiourea derivatives (3a-3n) were synthesized and characterized by NMR, FTIR and X-ray crystallographic techniques. The synthesized compounds displayed varying inhibition activities on both acetylcholineterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Among all compounds, 3b and 3e were potent inhibitors of AChE (IC50â¯Â±â¯SEMâ¯=â¯8.92â¯Â±â¯1.03â¯Î¼M) and BuChE (IC50â¯Â±â¯SEMâ¯=â¯6.96â¯Â±â¯0.961â¯Î¼M) respectively. Enzyme kinetic studies showed that 3b exhibited uncompetitive binding with AChE while 3e demonstrated a mixed inhibition of BuChE. Molecular docking studies on AChE showed that 3b got binding interaction with Trp86 and Tyr337 while 3e showed binding affinity with Trp82 and His438 when docked with BuChE. The obtained results indicated that these thiourea derivatives could be considered as potential candidates to treat AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Biological Macromolecules - Volume 116, September 2018, Pages 144-150
Journal: International Journal of Biological Macromolecules - Volume 116, September 2018, Pages 144-150
نویسندگان
Fayaz Ali Larik, Muhammad Shakil Shah, Aamer Saeed, Hamid Saeed Shah, Pervaiz Ali Channar, Michael Bolte, Jamshed Iqbal,