期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 19, 期 3, 页码 1277-1284出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2010.12.008
关键词
alpha-Aminoalkylphosphonates; Human neutrophil elastase; Multicomponent reactions; Inhibitors library; Serine protease inhibitors
资金
- Ministry of Science and Higher Education [N405 342633]
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-Val(P)(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. (C) 2010 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据