{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:21:37Z","timestamp":1791163297325,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chinese National Natural Science Foundation","award":["81373330"],"award-info":[{"award-number":["81373330"]}]},{"name":"Chinese National Natural Science Foundation","award":["20130071110068"],"award-info":[{"award-number":["20130071110068"]}]},{"name":"Specialized Research Fund for the Doctoral Program of Higher Education, Chinese Ministry of Education","award":["81373330"],"award-info":[{"award-number":["81373330"]}]},{"name":"Specialized Research Fund for the Doctoral Program of Higher Education, Chinese Ministry of Education","award":["20130071110068"],"award-info":[{"award-number":["20130071110068"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Millions of people worldwide suffer from acute or chronic liver inflammation caused by the hepatitis C virus (HCV). Metal ion chelators have achieved widespread success in the development of antiviral drugs. Some inhibitors with metal ion chelating structures have been proven to have good inhibitory activities on non-structural protein 5B (NS5B) polymerase. However, most of the reported metal ion chelators showed poor anti-HCV potency at the cellular level. Hence, we designed and synthesized a series of 3-hydroxyquinazoline-2,4(1H,3H)-dione derivatives with novel metal ion chelating structures. Typical compounds such as 21h, 21k, and 21t showed better anti-HCV activities than ribavirin with EC50 values less than 10 \u03bcM. 21t is currently known as one of the metal ion chelators with the best anti-HCV potency (EC50 = 2.0 \u03bcM) at the cellular level and has a better therapeutic index (TI &gt; 25) as compared to ribavirin and the reported compound 6. In the thermal shift assay, the representative compounds 21e and 21k increased the melting temperature (Tm) of NS5B protein solution by 1.6 \u00b0C and 2.1 \u00b0C, respectively, at the test concentration, indicating that these compounds may exert an anti-HCV effect by targeting NS5B. This speculation was also supported by our molecular docking studies and ultraviolet-visible (UV-Vis) spectrophotometry assay, in which the possibility of binding of 3-hydroxyquinazoline-2,4(1H,3H)-diones with Mg2+ in the NS5B catalytic center was observed.<\/jats:p>","DOI":"10.3390\/ijms23115930","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T08:41:33Z","timestamp":1653468093000},"page":"5930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Discovery of Novel 3-Hydroxyquinazoline-2,4(1H,3H)-Dione Derivatives: A Series of Metal Ion Chelators with Potent Anti-HCV Activities"],"prefix":"10.3390","volume":"23","author":[{"given":"Yang","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abudumijiti","family":"Aimaiti","sequence":"additional","affiliation":[{"name":"Shanghai Medical College, Fudan University, 130 Dongan Rd, Shanghai 200032, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyong","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Rd, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.jhep.2006.05.013","article-title":"The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide","volume":"45","author":"Perz","year":"2006","journal-title":"J. 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