کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1394902 1501094 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Design, synthesis and evaluation of 4-dimethylamine flavonoid derivatives as potential multifunctional anti-Alzheimer agents
ترجمه فارسی عنوان
طراحی، سنتز و ارزیابی مشتقات فلاونوئیدهای 4-دی متیل آمین به عنوان عوامل بالقوه چند منظوره ضد آلزایمر
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
چکیده انگلیسی


• Twelve 4-dimethylamine flavonoid derivatives were synthesized.
• They showed high inhibition activity for AChE and BChE.
• These compounds interacted at both CAS and PAS of AChE.
• They exhibited potent inhibition activity for ROS and Aβ aggregation.
• 6d significantly protected PC12 neurons against H2O2-induced cell death.

A new series of 4-dimethylamine flavonoid derivatives were designed and synthesized as potential multifunctional anti-Alzheimer agents. The inhibition of cholinesterase activity, self-induced β-amyloid (Aβ) aggregation, and antioxidant activity by these derivatives was investigated. Most of the compounds exhibited potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. A Lineweaver–Burk plot and molecular modeling study showed that these compounds targeted both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. The derivatives showed potent self-induced Aβ aggregation inhibition and peroxyl radical absorbance activity. Moreover, compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations. Thus, these compounds could become multifunctional agents for further development for the treatment of AD.

4-Dimethylamino flavonoid derivatives were synthesized as potential multi-functional anti-Alzheimer agents, they showed potent inhibition activity for cholinesterase, anti-oxidation and anti-Aβ aggregation activities. Molecular modeling study and kinetic analysis showed that these compounds interacted at both catalytic active site and peripheral anionic site of AChE. Compound 6d significantly protected PC12 neurons against H2O2-induced cell death at low concentrations.Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Medicinal Chemistry - Volume 122, 21 October 2016, Pages 17–26
نویسندگان
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