کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10585939 981382 2011 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
New cholesterol esterase inhibitors based on rhodanine and thiazolidinedione scaffolds
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
New cholesterol esterase inhibitors based on rhodanine and thiazolidinedione scaffolds
چکیده انگلیسی
We present a new class of inhibitors of pancreatic cholesterol esterase (CEase) based on 'priviledged' 5-benzylidenerhodanine and 5-benzylidene-2,4-thiazolidinedione structural scaffolds. The lead structures (5-benzylidenerhodanine 4a and 5-benzylidene-2,4-thiazolidinedione 4b) were identified in an in-house screening and these inhibited CEase with some selectivity over another serine hydrolase, acetylcholinesterase (AChE) (4a, CEase IC50 = 1.76 μM vs AChE IC50 = 5.14 μM and 4b, CEase IC50 = 5.89 μM vs AChE IC50 >100 μM). A small library of analogs (5a-10a) containing a core amino acid in place of the glycerol group of the lead structures, was prepared to explore other potential binding interaction with CEase. These analogs inhibited CEase with IC50 values ranging from 1.44 to 85 μM, with the majority exhibiting some selectivity for CEase versus AChE. The most potent compound of the library (10a) had 17-fold selectivity over AChE. We also report molecular docking (with CEase) and detailed kinetic analysis on the amino acid analogs to further understand the associated structure-activity relationships.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 24, 15 December 2011, Pages 7453-7463
نویسندگان
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