کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361117 981457 2008 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
New tacrine-dihydropyridine hybrids that inhibit acetylcholinesterase, calcium entry, and exhibit neuroprotection properties
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
New tacrine-dihydropyridine hybrids that inhibit acetylcholinesterase, calcium entry, and exhibit neuroprotection properties
چکیده انگلیسی

In this communication, we describe the synthesis and biological evaluation of tacripyrimedones 1–5, a series of new tacrine-1,4-dihydropyridine hybrids bearing the general structure of 11-amino-12-aryl-3,3-dimethyl-3,4,5,7,8,9,10,12-octahydrodibenzo[b,g][1,8]naphthyridine-1(2H)-one. These multifunctional compounds are moderately potent and selective AChEIs, with no activity toward BuChE. Kinetic analysis and molecular modeling studies point out that the new compounds preferentially bind the peripheral anionic site of AChE. In addition, compounds 1–5 show an excellent neuroprotective profile, and a moderate blocking effect of L-type voltage-dependent calcium channels due to the mitigation of [Ca2+] elevation elicited by K+ depolarization. Therefore, they represent a new family of molecules with potential therapeutic application for the treatment of Alzheimer’s disease.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 16, Issue 16, 15 August 2008, Pages 7759–7769
نویسندگان
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