Abstract
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.
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Selected References
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- Balzarini J., Holy A., Jindrich J., Naesens L., Snoeck R., Schols D., De Clercq E. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates: potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxypropyl)-2,6-diaminopurine. Antimicrob Agents Chemother. 1993 Feb;37(2):332–338. doi: 10.1128/aac.37.2.332. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boender P. J., Schalm S. W., Heijtink R. A. Detection of integration during active replication of hepatitis B virus in the liver. J Med Virol. 1985 May;16(1):47–54. doi: 10.1002/jmv.1890160107. [DOI] [PubMed] [Google Scholar]
- De Clercq E. Broad-spectrum anti-DNA virus and anti-retrovirus activity of phosphonylmethoxyalkylpurines and -pyrimidines. Biochem Pharmacol. 1991 Aug 8;42(5):963–972. doi: 10.1016/0006-2952(91)90276-b. [DOI] [PubMed] [Google Scholar]
- De Clercq E. Therapeutic potential of phosphonylmethoxyalkylpurines and -pyrimidines as antiviral agents. Drugs Exp Clin Res. 1990;16(7):319–326. [PubMed] [Google Scholar]
- Heijtink R. A., De Wilde G. A., Kruining J., Berk L., Balzarini J., De Clercq E., Holy A., Schalm S. W. Inhibitory effect of 9-(2-phosphonylmethoxyethyl)-adenine (PMEA) on human and duck hepatitis B virus infection. Antiviral Res. 1993 Jun;21(2):141–153. doi: 10.1016/0166-3542(93)90050-s. [DOI] [PubMed] [Google Scholar]
- Korba B. E., Milman G. A cell culture assay for compounds which inhibit hepatitis B virus replication. Antiviral Res. 1991 Mar-Apr;15(3):217–228. doi: 10.1016/0166-3542(91)90068-3. [DOI] [PubMed] [Google Scholar]
- Sells M. A., Chen M. L., Acs G. Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1005–1009. doi: 10.1073/pnas.84.4.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yokota T., Konno K., Chonan E., Mochizuki S., Kojima K., Shigeta S., de Clercq E. Comparative activities of several nucleoside analogs against duck hepatitis B virus in vitro. Antimicrob Agents Chemother. 1990 Jul;34(7):1326–1330. doi: 10.1128/aac.34.7.1326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yokota T., Mochizuki S., Konno K., Mori S., Shigeta S., De Clercq E. Inhibitory effects of selected antiviral compounds on human hepatitis B virus DNA synthesis. Antimicrob Agents Chemother. 1991 Feb;35(2):394–397. doi: 10.1128/aac.35.2.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Wilde G. A., Heijtink R. A. Immuno disc assay for screening duck hepatitis B surface antigen in serum, liver tissue and cultured hepatocytes. J Virol Methods. 1993 Jun;43(1):41–51. doi: 10.1016/0166-0934(93)90088-9. [DOI] [PubMed] [Google Scholar]