کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1365467 981562 2006 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis of new class dipeptide analogues with improved permeability and antithrombotic activity
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis of new class dipeptide analogues with improved permeability and antithrombotic activity
چکیده انگلیسی

3-(S)-1,2,3,4-Tetrahydro-β-carboline-3-carboxylic acid isolated from A. Chinese G. Don was found to possess moderate anti-aggregation activity, but with poor bioavailability. To improve its pharmacological property, we designed and synthesized a series of novel dipeptide analogues by incorporating tetrahydro-β-carboline-3-carboxylic acid skeleton as an amino acid surrogate (∗Trp). It turned out these dipeptide analogues exhibited good membrane permeability based on in vitro Caco-2 cell monolayers permeability assay. As a result, the overall biological properties of these molecules were significantly improved depending on the nature of the amino acid residues introduced onto the 3-position of the tetrahydro-β-carboline moiety. It was very interesting to notice that these dipeptide analogues (5b,c,h,i,n,o,p,q) displayed a remarkable dual antiaggregatory activity in both of ADP- and PAF-induced platelet aggregation assay, and their aggregation response was significantly higher than that of aspirin (p < 0.01). In addition, these dipeptide analogues were observed for the dose-dependent antithrombotic effect using in vivo rat arterial thrombosis model. The potency of antithrombotic activity of 5h,i,n,p was significantly higher than that of aspirin (n = 12, p < 0.01) at equal dose (5 μmol/kg).

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 14, Issue 14, 15 July 2006, Pages 4761–4774
نویسندگان
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