title: A new class of pyrimidine nucleosides: inhibitors of hepatitis B and C viruses.
abstract: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are major health threats worldwide leading to liver cirrhosis, liver cancer and mortality. Herein, we report a new category of dideoxy pyrimidine nucleosides possessing a 4'-carboxyl (or carboxymethyl) function (7-9, 13, 16, 17), which are discovered as potential antiviral agents. For the first time, these nucleosides are recognized to be inhibitors of HBV and/or HCV replication. Among 4'-carboxy compounds, 3',4'-didehydrothymidine (16) was most effective against DHBV, HBV and HCV. Modification of the 4'-position in compound 7 from a carboxyl to carboxymethyl group (17) did not affect the anti-HBV activity but greatly increased the anti-HCV activity. Importantly, 17 yielded synergistic antiviral effect when combined with ribavirin without toxicity. The activity exhibited by a single agent towards both hepatitis viruses and no detectable in vitro cytotoxicity make this new class of compounds of interest.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Shakya
authors.forename: Satish
authors.initials: S
authors.lastname: Vedi
authors.forename: Chao
authors.initials: C
authors.lastname: Liang
authors.forename: Babita
authors.initials: B
authors.lastname: Agrawal
authors.forename: D Lorne
authors.initials: DL
authors.lastname: Tyrrell
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000187:drug effects*; D006509:Hepatitis B / Q000188:drug therapy / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D006801:Humans; D008099:Liver / Q000821:virology; D011741:Pyrimidine Nucleosides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides