کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10583795 | 981310 | 2014 | 16 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Design, synthesis and evaluation of novel tacrine-(β-carboline) hybrids as multifunctional agents for the treatment of Alzheimer's disease
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کلمات کلیدی
CHESABTSAβNFTbutyrylcholinesteraseCASBuChEAPPMTT - MTTβ-Amyloid - β-آمیلوئیدβ-carboline - β-کاربولینAntioxidant - آنتی اکسیدانACh - آهAChE - آهیAcetylcholine - استیل کولینAcetylcholinesterase - استیل کولین استرازAlzheimer’s disease - بیماری آلزایمرTacrine - تاکرینβ-Amyloid aggregation - تجمع β-آمیلوئیدNeurofibrillary tangle - خلط نوروفیبریلاCNS - دستگاه عصبی مرکزیPeripheral anionic site - سایت آنیونی محیطیcatalytic anionic site - سایت آنیونی کاتالیزورBBB - سد خونی مغزیBlood–brain barrier - سد خونی مغزیcentral nervous system - سیستم عصبی مرکزیmethyl thiazolyl tetrazolium - متیل تیزولیل تترازولیمMolecular Operating Environment - محیط عملیاتی مولکولیMetal chelator - ملت فلزیPAS - نهMOE - وزارت صنایعamyloid precursor protein - پروتئین پیش ماده آمیلوئیCholinesterases - کولین استراز
موضوعات مرتبط
مهندسی و علوم پایه
شیمی
شیمی آلی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Design, synthesis and evaluation of novel tacrine-(β-carboline) hybrids as multifunctional agents for the treatment of Alzheimer's disease Design, synthesis and evaluation of novel tacrine-(β-carboline) hybrids as multifunctional agents for the treatment of Alzheimer's disease](/preview/png/10583795.png)
چکیده انگلیسی
A series of tacrine-(β-carboline) hybrids (11a-q) were designed, synthesized and evaluated as multifunctional cholinesterase inhibitors against Alzheimer's disease (AD). In vitro studies showed that most of them exhibited significant potency to inhibit acetylcholinesterase (eeAChE and hAChE), butyrylcholinesterase (BuChE) and self-induced β-amyloid (Aβ) aggregation, Cu2+-induced Aβ (1-42) aggregation, and to chelate metal ions. Especially, 11l presented the greatest ability to inhibit cholinesterase (IC50, 21.6 nM for eeAChE, 63.2 nM for hAChE and 39.8 nM for BuChE), good inhibition of Aβ aggregation (65.8% at 20 μM) and good antioxidant activity (1.57 trolox equivalents). Kinetic and molecular modeling studies indicated that 11l was a mixed-type inhibitor, binding simultaneously to the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. In addition, 11l could chelate metal ions, reduce PC12 cells death induced by oxidative stress and penetrate the blood-brain barrier (BBB). These results suggested that 11l might be an excellent multifunctional agent for AD treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 21, 1 November 2014, Pages 6089-6104
Journal: Bioorganic & Medicinal Chemistry - Volume 22, Issue 21, 1 November 2014, Pages 6089-6104
نویسندگان
Jin-Shuai Lan, Sai-Sai Xie, Su-Yi Li, Long-Fei Pan, Xiao-Bing Wang, Ling-Yi Kong,