Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1985 Jul;28(1):84–89. doi: 10.1128/aac.28.1.84

Antiviral and antimetabolic activities of neplanocins.

E De Clercq
PMCID: PMC176315  PMID: 2994559

Abstract

Of a series of carbocyclic analogs of adenosine, in which the ribose moiety was replaced by a cyclopentenyl ring, neplanocin A, or (-)-9-[trans-2, trans-3-dihydroxy-4-(hydroxymethyl)cyclopent-4-enyl]adenine proved particularly effective in inhibiting the multiplication of DNA viruses (i.e., vaccinia), (-)RNA viruses (i.e., parainfluenza, measles, and vesicular stomatitis), and double-stranded RNA viruses (i.e., reo) in vitro in cell culture. Depending on the cells used, the MIC of neplanocin A for these viruses ranged from 0.01 to 4 micrograms/ml, and depending on the parameter used to assess toxicity for the host cell, the specificity index of neplanocin A ranged from 50 to 4,000. As postulated before for other adenosine analogs, neplanocin A may owe its antiviral action to inhibition of S-adenosylhomocysteine hydrolase, hence perturbation of transmethylation reactions. In vivo, neplanocin A afforded only marginal protection against a lethal infection of mice with vesicular stomatitis virus.

Full text

PDF
84

Selected References

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

  1. Bader J. P., Brown N. R., Chiang P. K., Cantoni G. L. 3-Deazaadenosine, an inhibitor of adenosylhomocysteine hydrolase, inhibits reproduction of Rous sarcoma virus and transformation of chick embryo cells. Virology. 1978 Sep;89(2):494–505. doi: 10.1016/0042-6822(78)90191-5. [DOI] [PubMed] [Google Scholar]
  2. Bodner A. J., Cantoni G. L., Chiang P. K. Anti-viral activity of 3-deazaadenosine and 5'-deoxy-5'-isobutylthio-3-deazaadenosine (3-deaza-SIBA). Biochem Biophys Res Commun. 1981 Jan 30;98(2):476–481. doi: 10.1016/0006-291x(81)90864-0. [DOI] [PubMed] [Google Scholar]
  3. Borchardt R. T., Keller B. T., Patel-Thombre U. Neplanocin A. A potent inhibitor of S-adenosylhomocysteine hydrolase and of vaccinia virus multiplication in mouse L929 cells. J Biol Chem. 1984 Apr 10;259(7):4353–4358. [PubMed] [Google Scholar]
  4. Bryson Y. J., Connor J. D. In vitro susceptibility of varicella zoster virus to adenine arabinoside and hypoxanthine arabinoside. Antimicrob Agents Chemother. 1976 Mar;9(3):540–543. doi: 10.1128/aac.9.3.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chiang P. K., Guranowski A., Segall J. E. Irreversible inhibition of S-adenosylhomocysteine hydrolase by nucleoside analogs. Arch Biochem Biophys. 1981 Mar;207(1):175–184. doi: 10.1016/0003-9861(81)90023-0. [DOI] [PubMed] [Google Scholar]
  6. DE Clercq E., Descamps J., DE Somer P., Holyacute A. (S)-9-(2,3-Dihydroxypropyl)adenine: An Aliphatic Nucleoside Analog with Broad-Spectrum Antiviral Activity. Science. 1978 May 5;200(4341):563–565. doi: 10.1126/science.200.4341.563. [DOI] [PubMed] [Google Scholar]
  7. De Cercq E., Luczak M. Fluoroimidazoles as antiviral agents and inhibitors of polynucleotide biosynthesis. Life Sci. 1975 Jul 15;17(2):187–194. doi: 10.1016/0024-3205(75)90502-0. [DOI] [PubMed] [Google Scholar]
  8. De Clercq E., Bergstrom D. E., Holy A., Montgomery J. A. Broad-spectrum antiviral activity of adenosine analogues. Antiviral Res. 1984 Jun;4(3):119–133. doi: 10.1016/0166-3542(84)90012-3. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. De Clercq E., Holy A. Antiviral activity of aliphatic nucleoside analogues: structure-function relationship. J Med Chem. 1979 May;22(5):510–513. doi: 10.1021/jm00191a010. [DOI] [PubMed] [Google Scholar]
  11. Gephart J. F., Lerner A. M. Comparison of the effects of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate against herpes simplex virus, varicella-zoster virus, and cytomegalovirus with their effects on cellular deoxyribonucleic acid synthesis. Antimicrob Agents Chemother. 1981 Jan;19(1):170–178. doi: 10.1128/aac.19.1.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Giziewicz J., De Clercq E., Luczak M., Shugar D. Antiviral and antimetabolic activities of formycin and its N1-, N2-, 2'-O- and 3'-O-methylated derivatives. Biochem Pharmacol. 1975 Oct 1;24(19):1813–1817. doi: 10.1016/0006-2952(75)90462-1. [DOI] [PubMed] [Google Scholar]
  13. Guranowski A., Montgomery J. A., Cantoni G. L., Chiang P. K. Adenosine analogues as substrates and inhibitors of S-adenosylhomocysteine hydrolase. Biochemistry. 1981 Jan 6;20(1):110–115. doi: 10.1021/bi00504a019. [DOI] [PubMed] [Google Scholar]
  14. Hayashi M., Yaginuma S., Muto N., Tsujino M. Structures of neplanocins, new antitumor antibiotics. Nucleic Acids Symp Ser. 1980;(8):s65–s67. [PubMed] [Google Scholar]
  15. Hayashi M., Yaginuma S., Yoshioka H., Nakatsu K. Studies on neplanocin A, new antitumor antibiotic. II. Structure determination. J Antibiot (Tokyo) 1981 Jun;34(6):675–680. doi: 10.7164/antibiotics.34.675. [DOI] [PubMed] [Google Scholar]
  16. Montgomery J. A., Clayton S. J., Thomas H. J., Shannon W. M., Arnett G., Bodner A. J., Kion I. K., Cantoni G. L., Chiang P. K. Carbocyclic analogue of 3-deazaadenosine: a novel antiviral agent using S-adenosylhomocysteine hydrolase as a pharmacological target. J Med Chem. 1982 Jun;25(6):626–629. doi: 10.1021/jm00348a004. [DOI] [PubMed] [Google Scholar]
  17. Shipman C., Jr, Smith S. H., Carlson R. H., Drach J. C. Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures. Antimicrob Agents Chemother. 1976 Jan;9(1):120–127. doi: 10.1128/aac.9.1.120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Yaginuma S., Muto N., Tsujino M., Sudate Y., Hayashi M., Otani M. Studies on neplanocin A, new antitumor antibiotic. I. Producing organism, isolation and characterization. J Antibiot (Tokyo) 1981 Apr;34(4):359–366. doi: 10.7164/antibiotics.34.359. [DOI] [PubMed] [Google Scholar]
  19. de Clercq E., Montgomery J. A. Broad-spectrum antiviral activity of the carbocyclic analog of 3-deazaadenosine. Antiviral Res. 1983 Mar;3(1):17–24. doi: 10.1016/0166-3542(83)90011-6. [DOI] [PubMed] [Google Scholar]

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

RESOURCES