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. 1988 Dec;32(12):1904–1906. doi: 10.1128/aac.32.12.1904

Analogs of 5-methylthioribose, a novel class of antiprotozoal agents.

M K Riscoe 1, A J Ferro 1, J H Fitchen 1
PMCID: PMC176044  PMID: 2854458

Abstract

Since drug resistance and toxicity limit the use of available antiprotozoal agents, it is important that new drugs be developed as soon as possible. In this study, the method by which several protozoa degrade 5'-methylthioadenosine (MTA) was shown to differ from MTA catabolism in human cells. To exploit this metabolic difference, two analogs of methylthioribose (MTR), an MTA catabolite, were synthesized and found to be cytocidal to Plasmodium falciparum, Giardia lamblia, and Ochromonas malhamensis in vitro. In contrast, these analogs had no effect on cultured mammalian cells. Analogs of MTR represent a potential new class of antiprotozoal drugs.

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Selected References

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  1. Backlund P. S., Jr, Smith R. A. Methionine synthesis from 5'-methylthioadenosine in rat liver. J Biol Chem. 1981 Feb 25;256(4):1533–1535. [PubMed] [Google Scholar]
  2. Borchardt R. T., Huber J. A., Wu Y. S. A convenient preparation of S-adenosylhomocysteine and related compounds. J Org Chem. 1976 Feb 6;41(3):565–567. doi: 10.1021/jo00865a038. [DOI] [PubMed] [Google Scholar]
  3. Burgess A. W., Wilson E. M., Metcalf D. Stimulation by human placental conditioned medium of hemopoietic colony formation by human marrow cells. Blood. 1977 Apr;49(4):573–583. [PubMed] [Google Scholar]
  4. Campbell W. C. The chemotherapy of parasitic infections. J Parasitol. 1986 Feb;72(1):45–61. [PubMed] [Google Scholar]
  5. Coward J. K., Motola N. C., Moyer J. D. Polyamine biosynthesis in rat prostate. Substrate and inhibitor properties of 7-deaza analogues of decarboxylated S-adenosylmethionine and 5'-methylthioadenosine. J Med Chem. 1977 Apr;20(4):500–505. doi: 10.1021/jm00214a008. [DOI] [PubMed] [Google Scholar]
  6. Desjardins R. E., Canfield C. J., Haynes J. D., Chulay J. D. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother. 1979 Dec;16(6):710–718. doi: 10.1128/aac.16.6.710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ferro A. J., Barrett A., Shapiro S. K. 5-Methylthioribose kinase. A new enzyme involved in the formation of methionine from 5-methylthioribose. J Biol Chem. 1978 Sep 10;253(17):6021–6025. [PubMed] [Google Scholar]
  8. Ferro A. J., Barrett A., Shapiro S. K. Kinetic properties and the effect of substrate analogues on 5'-methylthioadenosine nucleosidase from Escherichia coli. Biochim Biophys Acta. 1976 Jul 8;438(2):487–494. doi: 10.1016/0005-2744(76)90264-3. [DOI] [PubMed] [Google Scholar]
  9. Ferro A. J., Marchitto K. S. 5-Methylthioribose kinase (Enterobacter aerogenes). Methods Enzymol. 1983;94:361–364. doi: 10.1016/s0076-6879(83)94065-x. [DOI] [PubMed] [Google Scholar]
  10. Kushad M. M., Richardson D. G., Ferro A. J. 5-Methylthioribose kinase activity in plants. Biochem Biophys Res Commun. 1982 Sep 16;108(1):167–173. doi: 10.1016/0006-291x(82)91846-0. [DOI] [PubMed] [Google Scholar]
  11. Kushad M. M., Richardson D. G., Ferro A. J. Intermediates in the recycling of 5-methylthioribose to methionine in fruits. Plant Physiol. 1983 Oct;73(2):257–261. doi: 10.1104/pp.73.2.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Oliver J. M., Paterson A. R. Nucleoside transport. I. A mediated process in human erythrocytes. Can J Biochem. 1971 Feb;49(2):262–270. doi: 10.1139/o71-038. [DOI] [PubMed] [Google Scholar]
  13. Pegg A. E., Williams-Ashman H. G. Phosphate-stimulated breakdown of 5'-methylthioadenosine by rat ventral prostate. Biochem J. 1969 Nov;115(2):241–247. doi: 10.1042/bj1150241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Peters W. The problem of drug resistance in malaria. Parasitology. 1985 Apr;90(Pt 4):705–715. doi: 10.1017/s003118200005232x. [DOI] [PubMed] [Google Scholar]
  15. Riscoe M. K., Ferro A. J. 5-Methylthioribose. Its effects and function in mammalian cells. J Biol Chem. 1984 May 10;259(9):5465–5471. [PubMed] [Google Scholar]
  16. Sanderson A., Walliker D., Molez J. F. Enzyme typing of Plasmodium falciparum from African and some other Old World countries. Trans R Soc Trop Med Hyg. 1981;75(2):263–267. doi: 10.1016/0035-9203(81)90331-x. [DOI] [PubMed] [Google Scholar]
  17. Schlenk F., Zydek-Cwick C. R., Dainko J. L. 5'-Methylthioadenosine and related compounds as precursors of S-adenosylmethionine in yeast. Biochim Biophys Acta. 1973 Sep 14;320(2):357–362. doi: 10.1016/0304-4165(73)90316-4. [DOI] [PubMed] [Google Scholar]
  18. Shapiro S. K., Barrett A. 5-Methylthioribose as a precursor of the carbon chain of methionine. Biochem Biophys Res Commun. 1981 Sep 16;102(1):302–307. doi: 10.1016/0006-291x(81)91521-7. [DOI] [PubMed] [Google Scholar]
  19. Stanley E. R., Bradley T. R., Sumner M. A. Properties of the mouse embryo conditioned medium factor(s) stimulationg colony formation by mouse bone marrow cells grown in vitro. J Cell Physiol. 1971 Oct;78(2):301–317. doi: 10.1002/jcp.1040780219. [DOI] [PubMed] [Google Scholar]
  20. Sugimoto Y., Toraya T., Fukui S. Studies on metabolic role of 5'-Methylthioadenosine in Ochromonas malhamensis and other microorganisms. Arch Microbiol. 1976 Jun;108(2):175–182. doi: 10.1007/BF00428948. [DOI] [PubMed] [Google Scholar]
  21. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  22. Williams-Ashman H. G., Seidenfeld J., Galletti P. Trends in the biochemical pharmacology of 5'-deoxy-5'-methylthioadenosine. Biochem Pharmacol. 1982 Feb 1;31(3):277–288. doi: 10.1016/0006-2952(82)90171-x. [DOI] [PubMed] [Google Scholar]
  23. Wyler D. J. Malaria--resurgence, resistance, and research. (First of two parts). N Engl J Med. 1983 Apr 14;308(15):875–878. doi: 10.1056/NEJM198304143081505. [DOI] [PubMed] [Google Scholar]

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