期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 22, 期 22, 页码 6952-6956出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.08.120
关键词
Coxsackievirus B3; 3C protease; Enzyme inhibitors
资金
- Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea [A090125]
- Institute of Medical System Engineering (iMSE) in the GIST, Korea
- Korea Health Promotion Institute [A090125] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Peptidomimetic anti-viral agents against Coxsackievirus B3 (CVB3) were developed using a strategy involving the inhibition of 3C protease (CVB3 3C(pro)), a target for CVB3-mediated myocarditis or pericarditis. In an attempt to improve the inhibitory activity against CVB3, a variety of hetero-aromatic groups were incorporated into the alpha,beta-unsaturated ester as Michael acceptor moiety, which is the position of interaction with the cysteine moiety in the P1' active site of CVB3 3C(pro). Among these hetero-aromatic groups, the quinoline analogs 9c and 9e, with IC50 values of 250 and 130 nM as determined from an enzyme assay, significantly inhibited the CVB3-mediated cell cytotoxicity, indicating parallel anti-viral activities. A comparison of the binding modes of the potent inhibitor 9e and the relatively weak inhibitor 9n was explored in a molecular docking study, which revealed that compound 9n lacked hydrogen bonds in its interactions with Gly129, 128, and 145. (C) 2012 Elsevier Ltd. All rights reserved.
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