Novel ring-expanded nucleoside analogs exhibit potent and selective inhibition of hepatitis B virus replication in cultured human hepatoblastoma cells.
Novel ring-expanded nucleoside (REN) analogs (1-3) containing 5:7 fused ring systems as the heterocyclic base were found to be potent and selective inhibitors of hepatitis B virus (HBV) replication in cultured human hepatoblastoma 2.2.15 cells. The most active compound, 6-amino-4,5-dihydro-8H-1-(beta-D-ribofuranosyl)imidazo[4,5-e][1,3]diazepine-4,8-dione (1), inhibited the synthesis of intracellular HBV replication intermediates and extracellular virion release in 2.2.15 cells with 50% effective concentration (EC50) of 0.604 and 0.131 microM, respectively. All three compounds had no effect on the synthesis of viral ribonucleic acids (RNA) in 2.2.15 cells. These compounds also exhibited low cellular toxicity in stationary and rapidly growing cell systems.
Sood
Ramesh K
RK
W.W. Karakawa Microbial Pathogenesis Laboratory, Nabi, Rockville, MD 20852, USA.
Bhadti
Vishweshwar S
VS
Fattom
Ali I
AI
Naso
Robert B
RB
Korba
Brent E
BE
Kern
Earl R
ER
Chen
Huan-Ming
HM
Hosmane
Ramachandra S
RS
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006509:Hepatitis B / Q000821:virology; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D018197:Hepatoblastoma; D006801:Humans; D008113:Liver Neoplasms; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D009705:Nucleosides