Novel ring-expanded nucleoside analogs exhibit potent and selective inhibition of hepatitis B virus replication in cultured human hepatoblastoma cells

• Published in: Antiviral research 2002-02, Vol.53 (2), p.159-164
• Main Authors: Sood, Ramesh K, Bhadti, Vishweshwar S, Fattom, Ali I, Naso, Robert B, Korba, Brent E, Kern, Earl R, Chen, Huan-Ming, Hosmane, Ramachandra S
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Biological and medical sciences; Hepatitis B - virology; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - physiology; Hepatoblastoma; hepatoblastoma cells; Human hepatoblastoma cell line; Humans; In vitro HBV inhibition; Liver Neoplasms; Low toxicity in stationary and fast-growing cell systems; Medical sciences; Nucleosides - chemical synthesis; Nucleosides - chemistry; Nucleosides - pharmacology; Pharmacology. Drug treatments; Ring-expanded nucleoside analogs; Tumor Cells, Cultured; Virus Replication - drug effects
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/S0166-3542(01)00204-2

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-8 H-1-(β- 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 (EC 50) of 0.604 and 0.131 μM, 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.