Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1987 Jan;31(1):21–26. doi: 10.1128/aac.31.1.21

Activity of (+)-cyclaradine (Sch 31172) against herpes simplex virus in vitro and in vivo.

J Schwartz, M Ostrander, N J Butkiewicz, M Lieberman, C Lin, J Lim, G H Miller
PMCID: PMC174644  PMID: 3032089

Abstract

(+)-Cyclaradine (Sch 31172) is the carbocyclic derivative of adenosine arabinoside (9-beta-D-arabinofuranosyladenine). Because it is not deaminated by deaminase in serum, as is adenosine arabinoside, (+)-cyclaradine is about 2 to 5 times more active in vitro against herpes simplex virus. (+)-Cyclaradine has in vitro activity nearly equivalent to that of phosphonoformate but is significantly less active than acycloguanosine (acyclovir; ACV), trifluorothymidine, or 9-(1,3-dihydroxy-2-propoxymethyl)guanine. The absolute ratios of in vitro activities are difficult to determine because of variability among virus strains, inoculum size, and dependence on the tissue culture cell line in which the comparative test is carried out. (+)-Cyclaradine is active against TK-, ACV-resistant mutants. In the guinea pig model of vaginal herpes simplex virus infection, (+)-cyclaradine is only slightly less active than ACV when both molecules are nearly equivalently bioavailable; thus, the large difference in activity seen in vitro is not reflected in this in vivo model system.

Full text

PDF
21

Selected References

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

  1. Bennett L. L., Jr, Allan P. W., Hill D. L. Metabolic studies with carbocyclic analogs of purine nucleosides. Mol Pharmacol. 1968 May;4(3):208–217. [PubMed] [Google Scholar]
  2. De Clercq E. Comparative efficacy of antiherpes drugs in different cell lines. Antimicrob Agents Chemother. 1982 Apr;21(4):661–663. doi: 10.1128/aac.21.4.661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. De Clercq E., Descamps J., Verhelst G., Walker R. T., Jones A. S., Torrence P. F., Shugar D. Comparative efficacy of antiherpes drugs against different strains of herpes simplex virus. J Infect Dis. 1980 May;141(5):563–574. doi: 10.1093/infdis/141.5.563. [DOI] [PubMed] [Google Scholar]
  4. Elion G. B., Furman P. A., Fyfe J. A., de Miranda P., Beauchamp L., Schaeffer H. J. Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl) guanine. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5716–5720. doi: 10.1073/pnas.74.12.5716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Field H., McMillan A., Darby G. The sensitivity of acyclovir-resistant mutants of herpes simplex virus to other antiviral drugs. J Infect Dis. 1981 Feb;143(2):281–285. doi: 10.1093/infdis/143.2.281. [DOI] [PubMed] [Google Scholar]
  6. Fraser-Smith E. B., Smee D. F., Matthews T. R. Efficacy of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanine against primary and recrudescent genital herpes simplex virus type 2 infections in guinea pigs. Antimicrob Agents Chemother. 1983 Dec;24(6):883–887. doi: 10.1128/aac.24.6.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Furman P. A., de Miranda P., St Clair M. H., Elion G. B. Metabolism of acyclovir in virus-infected and uninfected cells. Antimicrob Agents Chemother. 1981 Oct;20(4):518–524. doi: 10.1128/aac.20.4.518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fyfe J. A., Keller P. M., Furman P. A., Miller R. L., Elion G. B. Thymidine kinase from herpes simplex virus phosphorylates the new antiviral compound, 9-(2-hydroxyethoxymethyl)guanine. J Biol Chem. 1978 Dec 25;253(24):8721–8727. [PubMed] [Google Scholar]
  9. Harmenberg J., Wahren B. Influence of cell culture conditions on the inhibition of herpes simplex virus type 1 replication by acyclovir. Intervirology. 1982;17(4):215–221. doi: 10.1159/000149291. [DOI] [PubMed] [Google Scholar]
  10. Hsiung G. D., Mayo D. R., Lucia H. L., Landry M. L. Genital herpes: pathogenesis and chemotherapy in the guinea pig model. Rev Infect Dis. 1984 Jan-Feb;6(1):33–50. doi: 10.1093/clinids/6.1.33. [DOI] [PubMed] [Google Scholar]
  11. Jamieson A. T., Subak-Sharpe J. H. Interallelic complementation of mutants of herpes simplex virus deficient in deoxypyrimidine kinase activity. Virology. 1978 Mar;85(1):109–117. doi: 10.1016/0042-6822(78)90415-4. [DOI] [PubMed] [Google Scholar]
  12. Kern E. R. Acyclovir treatment of experimental genital herpes simplex virus infections. Am J Med. 1982 Jul 20;73(1A):100–108. doi: 10.1016/0002-9343(82)90073-0. [DOI] [PubMed] [Google Scholar]
  13. Martin J. C., Dvorak C. A., Smee D. F., Matthews T. R., Verheyden J. P. 9-[(1,3-Dihydroxy-2-propoxy)methyl]guanine: a new potent and selective antiherpes agent. J Med Chem. 1983 May;26(5):759–761. doi: 10.1021/jm00359a023. [DOI] [PubMed] [Google Scholar]
  14. Myerson D., Hsiung G. D. Prophylactic and therapeutic treatment with acyclovir of genital herpes in the guinea pig. Proc Soc Exp Biol Med. 1983 Nov;174(2):147–152. doi: 10.3181/00379727-174-41717. [DOI] [PubMed] [Google Scholar]
  15. Oberg B. Antiviral effects of phosphonoformate (PFA, foscarnet sodium). Pharmacol Ther. 1982;19(3):387–415. doi: 10.1016/0163-7258(82)90074-2. [DOI] [PubMed] [Google Scholar]
  16. Plunkett W., Cohen S. S. Two approaches that increase the activity of analogs of adenine nucleosides in animal cells. Cancer Res. 1975 Jun;35(6):1547–1554. [PubMed] [Google Scholar]
  17. Pronovost A. D., Lucia H. L., Dann P. R., Hsiung G. D. Effect of acyclovir on genital herpes in guinea pigs. J Infect Dis. 1982 Jun;145(6):904–908. doi: 10.1093/infdis/145.6.904. [DOI] [PubMed] [Google Scholar]
  18. Richards J. T., Kern E. R., Overall J. C., Jr, Glasgow L. A. Anti-herpesvirus activity of adenine arabinoside analogues in tissue culture and a genital infection of mice and guinea pigs. Antiviral Res. 1982 May;2(1-2):27–39. doi: 10.1016/0166-3542(82)90024-9. [DOI] [PubMed] [Google Scholar]
  19. Schnipper L. E., Crumpacker C. S. Resistance of herpes simplex virus to acycloguanosine: role of viral thymidine kinase and DNA polymerase loci. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2270–2273. doi: 10.1073/pnas.77.4.2270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Schwartz J., Elizan T. S. Growth of herpes simplex virus in transformed glial and neuronal cells in tissue culture: ultrastructural studies. J Neuropathol Exp Neurol. 1973 Apr;32(2):303–312. doi: 10.1097/00005072-197304000-00009. [DOI] [PubMed] [Google Scholar]
  21. Schwartz J., Whetsell W., Jr, Elizan T. S. Latent herpes simplex virus infection of mice. Infectious virus in homogenates of latently infected dorsal root ganglia. J Neuropathol Exp Neurol. 1978 Jan;37(1):45–55. doi: 10.1097/00005072-197801000-00004. [DOI] [PubMed] [Google Scholar]
  22. Shannon W. M., Arnett G., Drennen D. J. Lack of efficacy of 2-deoxy-D-glucose in the treatment of experimental herpes genitalis in guinea pigs. Antimicrob Agents Chemother. 1982 Mar;21(3):513–515. doi: 10.1128/aac.21.3.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shannon W. M., Westbrook L., Arnett G., Daluge S., Lee H., Vince R. Comparison of the efficacy of vidarabine, its carbocyclic analog (cyclaradine), and cyclaradine-5'-methoxyacetate in the treatment of herpes simplex virus type 1 encephalitis in mice. Antimicrob Agents Chemother. 1983 Oct;24(4):538–543. doi: 10.1128/aac.24.4.538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Vince R., Daluge S. Carbocyclic arabinosyladenine, an adenosine deaminase resistant antiviral agent. J Med Chem. 1977 Apr;20(4):612–613. doi: 10.1021/jm00214a040. [DOI] [PubMed] [Google Scholar]
  25. Vince R., Daluge S., Lee H., Shannon W. M., Arnett G., Schafer T. W., Nagabhushan T. L., Reichert P., Tsai H. Carbocyclic arabinofuranosyladenine (cyclaradine): efficacy against genital herpes in guinea pigs. Science. 1983 Sep 30;221(4618):1405–1406. doi: 10.1126/science.6684328. [DOI] [PubMed] [Google Scholar]
  26. Whitley R., Alford C., Hess F., Buchanan R. Vidarabine: a preliminary review of its pharmacological properties and therapeutic use. Drugs. 1980 Oct;20(4):267–282. doi: 10.2165/00003495-198020040-00002. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES