Antiviral activity of 5'-O-carbonate-2',3'-dideoxy-3'-thiacytidine prodrugs against hepatitis B virus in HepG2 2.2.15 cells.
The antiviral activities of lamivudine (3TC; 2',3'-dideoxy-3'-thiacytidine) and six 5'-O-carbonates of 3TC were determined by inhibition of hepatitis B virus (HBV) replication in HepG2 2.2.15 cells. HBV DNA in cell supernatants was quantified by real-time polymerase chain reaction (PCR). The results showed that 3TC-Etha was six times more active than 3TC and that 3TC-Buta, 3TC-Hexa and 3TC-Octa were approximately three times more active than 3TC. In contrast, 3TC-Penta and 3TC-Metha showed anti-HBV activity similar to that of the parent compound 3TC. In conclusion, 5'-O-carbonates of 3TC appear to be promising candidates as anti-HBV compounds. This modification could optimise the use of 3TC, a well-tolerated, effective and inexpensive drug, in monotherapy or combined therapy for chronic HBV infections as well as human immunodeficiency virus (HIV)/HBV co-infections.
Gagey
Dolores
D
Cátedra de Virología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, 4° Piso, Ciudad Autónoma de Buenos Aires 1113, Argentina.
Ravetti
Soledad
S
Castro
Eliana F
EF
Gualdesi
María Soledad
MS
Briñon
Margarita C
MC
Campos
Rodolfo H
RH
Cavallaro
Lucía V
LV
D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D003470:Culture Media / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006515:Hepatitis B virus / Q000187:drug effects*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
C482460:5'-O-carbamate-2',3'-dideoxythiacytidine; D000998:Antiviral Agents; D003470:Culture Media; D004279:DNA, Viral; D011355:Prodrugs; D003841:Deoxycytidine; D019259:Lamivudine