کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1361687 981469 2011 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phosphonic pseudopeptides as human neutrophil elastase inhibitors—a combinatorial approach
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Phosphonic pseudopeptides as human neutrophil elastase inhibitors—a combinatorial approach
چکیده انگلیسی

Here we present a simple and rapid method for the construction of phosphonic peptide mimetic inhibitor libraries—products of Ugi and Passerini multicomponent condensations—leading to the selection of new biologically active phosphonic pseudopeptides. As the starting isonitriles, 1-isocyanoalkylphosphonate diaryl ester derivatives were applied. The structure of the synthesized inhibitors was designed to target human neutrophil elastase, a serine protease whose uncontrolled activity may lead to development of several pathophysiological states such as rheumatoid arthritis, cystic fibrosis or tumor growth and invasion. After screening the inhibitory activity of our constructed libraries, the most active compounds were synthesized as single molecules. One of the obtained inhibitors, Cbz-Met-O-Met-ValP(OC6H4-p-Cl)2, displayed apparent second-order inhibition value at 40,105 M−1 s−1 as the diastereomers mixture. Inhibition potency and selectivity of action toward other serine proteases as well as the results of initial in vitro experiments regarding inhibitors influence on cancer cell proliferation are presented.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 19, Issue 3, 1 February 2011, Pages 1277–1284
نویسندگان
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