{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:07:52Z","timestamp":1793650072517,"version":"4.5.1"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T00:00:00Z","timestamp":1433376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>In this work, the relationship between cyclophilin A (CypA) and HCV prompted us to screen a series of small molecule CypA inhibitors which were previously reported by our group. Among them, compound 1, discovered as a non-immunosuppressive anti-HCV agent with an EC50 value of 0.67 \u03bcM in a virus assay, was selected for further study. Subsequent chemical modification by O-acylation led to a novel class of molecules, among which compound 25 demonstrated the most potent anti-HCV activity in the virus assay  (EC50 = 0.19 \u03bcM), but low cytotoxicity and hERG cardiac toxicity. The following studies (a solution stability assay and a simple pharmacokinetic test together with a CypA enzyme inhibition assay) preliminarily indicated that 25 was a prodrug of 1. To the best of our knowledge, 25 is probably the most potent currently reported small molecule anti-HCV agent acting via the CypA inhibitory mechanism. Consequently, our study has provided a new potential small molecule for curing HCV infection.<\/jats:p>","DOI":"10.3390\/molecules200610342","type":"journal-article","created":{"date-parts":[[2015,6,4]],"date-time":"2015-06-04T11:54:59Z","timestamp":1433418899000},"page":"10342-10359","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Discovery of Novel Small Molecule Anti-HCV Agents via the CypA Inhibitory Mechanism Using O-Acylation-Directed  Lead Optimization"],"prefix":"10.3390","volume":"20","author":[{"given":"Wenzhong","family":"Yan","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of New Drug Design, School of Pharmacy,  East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Qing","sequence":"additional","affiliation":[{"name":"Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University,  Beijing 100084, China"},{"name":"School of Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbing","family":"Mei","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of New Drug Design, School of Pharmacy,  East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Mao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of New Drug Design, School of Pharmacy,  East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Huang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of New Drug Design, School of Pharmacy,  East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of New Drug Design, School of Pharmacy,  East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hualiang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of New Drug Design, School of Pharmacy,  East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China"},{"name":"Drug Discovery and Design Center, Shanghai Institute of Materia Medica,  Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University,  Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linqi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of New Drug Design, School of Pharmacy,  East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cld.2009.11.009","article-title":"Epidemiology of hepatitis B and C viruses: A global overview","volume":"14","author":"Te","year":"2010","journal-title":"Clin. 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