{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T17:13:38Z","timestamp":1760548418188},"reference-count":40,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2007,7,1]],"date-time":"2007-07-01T00:00:00Z","timestamp":1183248000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2007,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Novel N\n            <jats:sup>4<\/jats:sup>\n            -hydroxy- and 5-methyl-modified \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -deoxycytidine analogues were synthesized and evaluated as anti-hepatitis B virus (HBV) agents. Their in vitro efficiencies were investigated in HepG2.2.15 cells stably transfected with HBV. \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -2\u2032,3\u2032-Didehydro-2\u2032,3\u2032-dideoxy-N\n            <jats:sup>4<\/jats:sup>\n            -hydroxycytidine (\u03b2-\n            <jats:sc>l<\/jats:sc>\n            -Hyd4C) was most effective in reducing secreted HBV DNA (50% effective concentration [EC\n            <jats:sub>50<\/jats:sub>\n            ], 0.03 \u03bcM), followed by \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -2\u2032,3\u2032-dideoxy-3\u2032-thia-N\n            <jats:sup>4<\/jats:sup>\n            -hydroxycytidine (EC\n            <jats:sub>50<\/jats:sub>\n            , 0.51 \u03bcM), \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -2\u2032,3\u2032-dideoxy-N\n            <jats:sup>4<\/jats:sup>\n            -hydroxycytidine (EC\n            <jats:sub>50<\/jats:sub>\n            , 0.55 \u03bcM), and \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -5-methyl-2\u2032-deoxycytidine (EC\n            <jats:sub>50<\/jats:sub>\n            , 0.9 \u03bcM). The inhibition of the presumed target, the HBV DNA polymerase, by the triphosphates of some of the \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -cytidine derivatives was also assessed. In accordance with the cell culture data, \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -Hyd4C triphosphate was the most active inhibitor, with a 50% inhibitory concentration of 0.21 \u03bcM. The cytotoxicities of some of the 4-NHOH-modified \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -nucleosides were dramatically lower than those of the corresponding cytidine analogues with the unmodified 4-NH\n            <jats:sub>2<\/jats:sub>\n            group. The 50% cytotoxic concentrations for \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -Hyd4C in HepG2 and HL-60 cells were 2,500 \u03bcM and 3,500 \u03bcM, respectively. In summary, our results demonstrate that at least \u03b2-\n            <jats:sc>l<\/jats:sc>\n            -Hyd4C can be recommended as a highly efficient and extremely selective inhibitor of HBV replication for further investigations.\n          <\/jats:p>","DOI":"10.1128\/aac.00001-07","type":"journal-article","created":{"date-parts":[[2007,4,3]],"date-time":"2007-04-03T00:54:34Z","timestamp":1175561674000},"page":"2523-2530","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Strong and Selective Inhibitors of Hepatitis B Virus Replication among Novel N\n            <sup>4<\/sup>\n            -Hydroxy- and 5-Methyl-\u03b2-\n            <scp>l<\/scp>\n            -Deoxycytidine Analogues"],"prefix":"10.1128","volume":"51","author":[{"given":"E.","family":"Matthes","sequence":"first","affiliation":[{"name":"Max-Delbru\u0308ck-Centrum fu\u0308r Molekulare Medizin, Robert-Ro\u0308ssle-Str. 10, 13092 Berlin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Funk","sequence":"additional","affiliation":[{"name":"Heinrich-Pette-Institut fu\u0308r Experimentelle Immunologie und Virologie, P.O. Box 201652, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"I.","family":"Krahn","sequence":"additional","affiliation":[{"name":"Max-Delbru\u0308ck-Centrum fu\u0308r Molekulare Medizin, Robert-Ro\u0308ssle-Str. 10, 13092 Berlin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Gaertner","sequence":"additional","affiliation":[{"name":"Max-Delbru\u0308ck-Centrum fu\u0308r Molekulare Medizin, Robert-Ro\u0308ssle-Str. 10, 13092 Berlin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"von Janta-Lipinski","sequence":"additional","affiliation":[{"name":"Max-Delbru\u0308ck-Centrum fu\u0308r Molekulare Medizin, Robert-Ro\u0308ssle-Str. 10, 13092 Berlin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Lin","sequence":"additional","affiliation":[{"name":"Heinrich-Pette-Institut fu\u0308r Experimentelle Immunologie und Virologie, P.O. 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