Inhibitory effects of acyclic nucleoside phosphonates on human hepatitis B virus and duck hepatitis B virus infections in tissue culture.
The inhibitory effects of the 9-(2-phosphonylmethoxyethyl)adenine-related compounds (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-adenine, (S)-9-(3-fluoro-2-phosphonylmethoxypropyl)adenine, (R)-9-(2-phosphonylmethoxypropyl)adenine, (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine, and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine on human hepatitis B virus replication in the human hepatoma cell line HepG2 2.2.15 and duck hepatitis B virus infection in primary duck hepatocytes were investigated. (R)-9-(2-phosphonylmethoxypropyl-2,6-diaminopurine had the lowest 50% inhibitory concentrations against hepatitis B virus and duck hepatitis B virus, 0.22 and 0.06 microM, respectively, i.e., two- to fivefold lower concentrations than required for (R)-9-(2-phosphonylmethoxypropyl)adenine and 9-(2-phosphonylmethoxyethyl)adenine. All compounds were not toxic in vitro at a concentration of 100 microM.
Heijtink
R A
RA
Department of Virology, Erasmus University Rotterdam, The Netherlands.
Kruining
J
J
de Wilde
G A
GA
Balzarini
J
J
de Clercq
E
E
Schalm
S W
SW
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000821:virology; D003596:Cytosine / Q000031:analogs & derivatives; D004372:Ducks; D015611:Hepatitis B Virus, Duck / Q000187:drug effects*; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000166:cytology / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology; D009705:Nucleosides / Q000494:pharmacology*; D063065:Organophosphonates / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D014407:Tumor Cells, Cultured
C090125:9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine; D000998:Antiviral Agents; D009705:Nucleosides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D011687:Purines; D003596:Cytosine; D000225:Adenine