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. 1991 Feb;35(2):394–397. doi: 10.1128/aac.35.2.394

Inhibitory effects of selected antiviral compounds on human hepatitis B virus DNA synthesis.

T Yokota 1, S Mochizuki 1, K Konno 1, S Mori 1, S Shigeta 1, E De Clercq 1
PMCID: PMC245016  PMID: 2024975

Abstract

By using an assay system based on a human hepatoblastoma cell line (HB611) that continuously synthesizes hepatitis B virus DNA, the following compounds were found to inhibit hepatitis B virus DNA synthesis at concentrations that were significantly lower than their minimum cytotoxic concentrations: 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, 9-(phosphonylmethoxyethyl)adenine, 2',3'-dideoxy-2',3'-didehydrocytidine, and 2',3'-dideoxycytidine. The most potent compound was PMEDAP (50% effective concentration, 0.02 micrograms/ml). The selective index, or ratio of the 50% cytotoxic concentration to 50% effective concentration, of PMEDAP was greater than 750.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arzuza O., García-Villalón D., Tabarés E., Gil-Fernández C., De Clercq E. Inhibition of African swine fever virus DNA synthesis by (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine. Biochem Biophys Res Commun. 1988 Jul 15;154(1):27–32. doi: 10.1016/0006-291x(88)90644-4. [DOI] [PubMed] [Google Scholar]
  2. Baba M., Pauwels R., Herdewijn P., De Clercq E., Desmyter J., Vandeputte M. Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro. Biochem Biophys Res Commun. 1987 Jan 15;142(1):128–134. doi: 10.1016/0006-291x(87)90460-8. [DOI] [PubMed] [Google Scholar]
  3. Balzarini J., Pauwels R., Herdewijn P., De Clercq E., Cooney D. A., Kang G. J., Dalal M., Johns D. G., Broder S. Potent and selective anti-HTLV-III/LAV activity of 2',3'-dideoxycytidinene, the 2',3'-unsaturated derivative of 2',3'-dideoxycytidine. Biochem Biophys Res Commun. 1986 Oct 30;140(2):735–742. doi: 10.1016/0006-291x(86)90793-x. [DOI] [PubMed] [Google Scholar]
  4. De Clercq E., Sakuma T., Baba M., Pauwels R., Balzarini J., Rosenberg I., Holý A. Antiviral activity of phosphonylmethoxyalkyl derivatives of purine and pyrimidines. Antiviral Res. 1987 Dec;8(5-6):261–272. doi: 10.1016/s0166-3542(87)80004-9. [DOI] [PubMed] [Google Scholar]
  5. Lee B., Luo W. X., Suzuki S., Robins M. J., Tyrrell D. L. In vitro and in vivo comparison of the abilities of purine and pyrimidine 2',3'-dideoxynucleosides to inhibit duck hepadnavirus. Antimicrob Agents Chemother. 1989 Mar;33(3):336–339. doi: 10.1128/aac.33.3.336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Lin J. C., DeClercq E., Pagano J. S. Novel acyclic adenosine analogs inhibit Epstein-Barr virus replication. Antimicrob Agents Chemother. 1987 Sep;31(9):1431–1433. doi: 10.1128/aac.31.9.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lin T. S., Schinazi R. F., Chen M. S., Kinney-Thomas E., Prusoff W. H. Antiviral activity of 2',3'-dideoxycytidin-2'-ene (2',3'-dideoxy-2',3'-didehydrocytidine) against human immunodeficiency virus in vitro. Biochem Pharmacol. 1987 Feb 1;36(3):311–316. doi: 10.1016/0006-2952(87)90287-5. [DOI] [PubMed] [Google Scholar]
  8. Lin T. S., Schinazi R. F., Prusoff W. H. Potent and selective in vitro activity of 3'-deoxythymidin-2'-ene (3'-deoxy-2',3'-didehydrothymidine) against human immunodeficiency virus. Biochem Pharmacol. 1987 Sep 1;36(17):2713–2718. doi: 10.1016/0006-2952(87)90253-x. [DOI] [PubMed] [Google Scholar]
  9. Price P. M., Banerjee R., Acs G. Inhibition of the replication of hepatitis B virus by the carbocyclic analogue of 2'-deoxyguanosine. Proc Natl Acad Sci U S A. 1989 Nov;86(21):8541–8544. doi: 10.1073/pnas.86.21.8541. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Shigeta S., Konno K., Yokota T., Nakamura K., De Clercq E. Comparative activities of several nucleoside analogs against influenza A, B, and C viruses in vitro. Antimicrob Agents Chemother. 1988 Jun;32(6):906–911. doi: 10.1128/aac.32.6.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Suzuki S., Lee B., Luo W., Tovell D., Robins M. J., Tyrrell D. L. Inhibition of duck hepatitis B virus replication by purine 2',3'-dideoxynucleosides. Biochem Biophys Res Commun. 1988 Nov 15;156(3):1144–1151. doi: 10.1016/s0006-291x(88)80752-6. [DOI] [PubMed] [Google Scholar]
  12. Tuttleman J. S., Pugh J. C., Summers J. W. In vitro experimental infection of primary duck hepatocyte cultures with duck hepatitis B virus. J Virol. 1986 Apr;58(1):17–25. doi: 10.1128/jvi.58.1.17-25.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ueda K., Tsurimoto T., Nagahata T., Chisaka O., Matsubara K. An in vitro system for screening anti-hepatitis B virus drugs. Virology. 1989 Mar;169(1):213–216. doi: 10.1016/0042-6822(89)90057-3. [DOI] [PubMed] [Google Scholar]
  14. Votruba I., Bernaerts R., Sakuma T., De Clercq E., Merta A., Rosenberg I., Holý A. Intracellular phosphorylation of broad-spectrum anti-DNA virus agent (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and inhibition of viral DNA synthesis. Mol Pharmacol. 1987 Oct;32(4):524–529. [PubMed] [Google Scholar]
  15. 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]

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