國家衛生研究院 NHRI:Item 3990099045/3392

NHRI > Institute of Biotechnology and Pharmaceutical Research > John Tsu-An Hsu > Periodical Articles > Item 3990099045/3392

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/3392

Title:	Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents
Authors:	Kuo, CJ;Shie, JJ;Fang, JM;Yen, GR;Hsu, JTA;Liu, HG;Tseng, SN;Chang, SC;Lee, CY;Shih, SR;Liang, PH
Contributors:	Division of Biotechnology and Pharmaceutical Research
Abstract:	Human enterovirus (EV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. A peptidomimetic inhibitor AG7088 was developed to inhibit the 3C protease of rhinovirus (a member of the family), a chymotrypsin-like protease required for viral replication, by forming a covalent bond with the active site Cys residue. In this study, we have prepared the recombinant 3C protease from EV71 (TW/2231/98), a particular strain which causes severe outbreaks in Asia, and developed inhibitors against the protease and the viral replication. For inhibitor design, the P3 group of AG7088, which is not interacting with the rhinovirus protease, was replaced with a series of cinnamoyl derivatives directly linked to P2 group through an amide bond to simplify the synthesis. While the replacement caused decreased potency, the activity can be largely improved by substituting the α,β-unsaturated ester with an aldehyde at the P1′ position. The best inhibitor 10b showed EC50 of 18 nM without apparent toxicity (CC50 > 25 μM). Our study provides potent inhibitors of the EV71 3C protease as anti-EV71 agents and facilitates the combinatorial synthesis of derivatives for further improving the inhibitory activity. ? 2008 Elsevier Ltd. All rights reserved.
Date:	2008-08-01
Relation:	Bioorganic and Medicinal Chemistry. 2008 Aug 1;16(15):7388-7398.
Link to:	http://dx.doi.org/10.1016/j.bmc.2008.06.015
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0968-0896&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000258749500033
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=48649105986
Appears in Collections:	[John Tsu-An Hsu] Periodical Articles

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