Hostname: page-component-76fb5796d-dfsvx Total loading time: 0 Render date: 2024-04-27T01:26:23.633Z Has data issue: false hasContentIssue false
  • English
  • Français

Metabolism by Schistosoma mansoni of a new schistosomicide: 2-[(1-methylpropyl)amino]-1-octanethiosulphuric acid

Published online by Cambridge University Press:  06 April 2009

M. L. O. Penido ,
D. L. Nelson ,
L. Q. Vieira ,
D. G. Watson  and
J. R. Kusel
M. L. O. Penido
Affiliation:
Departamento de Bioquímica-Imunologia-ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
D. L. Nelson
Affiliation:
Departamento de Bioquímica-Imunologia-ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
L. Q. Vieira
Affiliation:
Departamento de Bioquímica-Imunologia-ICB, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
D. G. Watson
Affiliation:
Dpartment of Pharmaceutical Sciences, University of Strathclyde, Glasgow, Scotland
J. R. Kusel
Affiliation:
Department of Biochemistry, University of Glasgow, Glasgow, Scotland
Get access Rights & Permissions [Opens in a new window]

Summary

In order to investigate the mode of action of a new class of schistosomicides, the N-alkylaminoalkanethiosulphuric acids, the ‘outer 35S] 2-[(1-methylpropyl)amino]-1-octanethiosulphuric acid was synthesized. Labelling studies of adult Schistosoma mansoni were performed in infected mice and in in vitro incubations. After a single oral dose of the drug to infected mice, 5 metabolites were detected by thin-layer chromatography in organic extracts of male and female adult schistosomes. In vitro studies showed that the same compounds were present in organic extracts obtained from adult male and female worms. One of these metabolites was identified by mass spectroscopy as being the dimeric disulphide derivative of the parent labelled thiosulphuric acid.

Keywords

aminoalkanethiosulphuric acidsBunte saltsschistosomicidesSchistosoma mansonischistosomiasis
Type
Research Article
Information
Parasitology , Volume 111 , Issue 2 , August 1995 , pp. 177 - 185
Copyright
Copyright © Cambridge University Press 1995

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Bell, E. J. & Smith, J. D. (1958). Cytological and histochemical criteria for evaluating development of trematodes and pseudophyllidean cestodes in vivoand in vitro. Parasitology 48, 131–48.CrossRefGoogle Scholar
Bueding, E., Dolan, P. & Leroy, J. P. (1982). The biochemical activity of oltipraz. Research Communications in Chemical Pathology and Pharmacology 37, 293–303.Google Scholar
Bueding, E. & Fisher, J. (1982). Metabolic requirements of schistosomes. Journal of Parasitology 68, 208–12.CrossRefGoogle ScholarPubMed
Chamberlain, J. P. (1979). Fluorographic detection of radioactivity in polyacrylamide gels with the water soluble fluor, sodium salicylate. Analytical Biochemistry 98, 132.CrossRefGoogle ScholarPubMed
Chappell, C. L. & Dresden, M. H. (1987). Purification of cysteine proteinases from adult Schistosoma mansoni. Archives of Biochemistry and Biophysics 256, 560–8.CrossRefGoogle ScholarPubMed
Clegg, J. A. & Smithers, S. R. (1972). The effect of immune rhesus monkey serum on Schistosoma mansoni during cultivation in vitro. International Journal for Parasitology 2, 79–98.CrossRefGoogle ScholarPubMed
Diekmam, J. & Djerassi, C. (1967). Mass spectrometry in structural and stereochemical problems. CXXV. Journal of Organic Chemistry 32, 1005–14.CrossRefGoogle Scholar
Doenhoff, M. J., Sabah, A. A. A., Fletcher, C., Webbe, G. & Bain, J. (1987). Evidence for an immune-dependent action of praziquantel on Schistosoma mansoni in mice. Transactions of the Royal Society of Tropical Medicine and Hygiene 81, 947–51.CrossRefGoogle ScholarPubMed
Frappier, F., Azoulay, M. & Leroy, J. P. (1988). Effect of oltipraz on the metabolism of glutathione in Schistosoma mansoni. Biochemical Pharmacology 37, 2846–66.CrossRefGoogle Scholar
Harnett, W. & Kusel, J. R. (1987). Increased exposure of parasite antigens at the surface of adult male Schistosoma mansoni exposed to praziquantel in vitro. Parasitology 93, 401–5.CrossRefGoogle Scholar
Holmberg, B. & Sorbo, B. (1959). Protective effect of beta-aminoethylthiosulphuric acid against ionizing radiation. Nature, London 183, 832.CrossRefGoogle ScholarPubMed
Jacobus, D. P., Klayman, D. L., Rothe, W., Greenan, M. M., Henderson, E. & Davidson, E. (1966). N-Substituted aminoethanethiosulphuric acids as potential anti-radiation agents. The Pharmacologist 8, 226.Google Scholar
Kelley, J. J., Hamilton, N. F. & Friedman, O. M. (1967). Studies on latent derivatives of aminoethanethiols as potentially selective cytoprotectants. III. Reactions of cysteamine-S-sulfate in biological media. Cancer Research 27, 143–7.Google Scholar
Laemmli, U. K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227, 680–5.CrossRefGoogle ScholarPubMed
Lawrence, J. D. (1973). The ingestion of red blood cells by Schistosoma mansoni. Journal of Parasitology 59, 60–3.CrossRefGoogle ScholarPubMed
Lennox, R. W. & Schiller, E. C. (1972). Changes in dry weight and glycogen content as criteria for measuring the post-cercarial growth and development of Schistosoma mansoni. Journal of Parasitology 58, 489–94.CrossRefGoogle Scholar
Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. (1951). Protein measurement with the folin phenol reagent. Journal of Biological Chemistry 193, 265–75.CrossRefGoogle ScholarPubMed
Mkoji, G. M., Smith, J. M. & Prichard, R. K. (1988 a). Antioxidant system in Schistosoma mansoni: correlation between susceptibility to oxidant killing and the levels of scavengers of hydrogen peroxide and oxygen radicals. International Journal for Parasitology 18, 661–6.CrossRefGoogle Scholar
Mkoji, G. M., Smith, J. R. & Prichard, R. K. (1988 b). Antioxidant system in Schistosoma mansoni: evidence for their role in protection of the adult worms against oxidant killing. International Journal for Parasitology 18, 667–73.CrossRefGoogle ScholarPubMed
Modha, J., Lambertucci, J. R., Doenhoff, M. J. & McLaren, D. J. (1990). Immune dependence of schistosomicidal chemotherapy: an ultrastructural study of Schistosoma mansoni adult worms exposed to praziquantel and immune serum in vivo. Parasite Immunology 12, 321–34.CrossRefGoogle ScholarPubMed
Morrison, D. D., Thompson, D. P., Semeyn, D. R. & Bennet, J. L. (1987). Acute effects of oltipraz on adult Schistosoma mansoni and its antagonism in vitro. Biochemical Pharmacology 36, 1169–71.CrossRefGoogle ScholarPubMed
Nelson, D. L. & Pellegrino, J. (1976). Schistosoma mansoni. Active derivatives of aminoethanethio-sulphuric acids. Revista do Institute de Medicina Tropical de Sãao Paulo 18, 365–70.Google Scholar
Penido, M. L. O., Nelson, D. L., Vieira, L. Q. & Coelho, P. M. Z. (1994). Schistosomicidal activity of alkylaminooctanethiosulphuric acids. Memórias do Institute Oswaldo Cruz 89, 595–602.CrossRefGoogle ScholarPubMed
Penido, M. L. O., Pilo-Veloso, D. & Nelson, D. L. (1990). Synthesis of potential schistosomicides: new 2-(alkylamino)-1-octanethiosulphuric acids. Journal of the Brazilian Chemistry Society 1, 35–9.CrossRefGoogle Scholar
Sabah, A. A., Fletcher, C., Webbe, G. & Doenhoff, M. J. (1985). Schistosoma mansoni: reduced efficacy of chemotherapy in infected T-cell-deprived mice. Experimental Parasitology 60, 348–54.CrossRefGoogle ScholarPubMed
Smithers, S. R. & Terry, R. J. (1965). The infection of laboratory hosts with cercariae of Schistosoma mansoni, and recovery of adult worms. Parasitology 55, 695.CrossRefGoogle ScholarPubMed
Tracy, J. W., Catto, B. A. & Webster, L. T. Jr. (1983). Reductive metabolism of niridazole by adult Schistosoma mansoni. Correlation with covalent drug binding to parasite macromolecules. Molecular Pharmacology 24, 291–9.Google ScholarPubMed
Westland, R. D., Holmes, J. L., Mouk, M. L., Marsh, D. D., Cooley, R. A. Jr & Dice, J. R. (1968). N-Substituted S-2-aminoethylthiosulfates as antiradiation agents. Journal of Medical Chemistry 11, 1190.CrossRefGoogle Scholar