Skip to main content
SpringerLink
Log in

Antimalarial activity of synthetic 1,2,4-trioxanes and cyclic peroxy ketals, a quantum similarity study

  • Published:
Journal of Computer-Aided Molecular Design Aims and scope Submit manuscript

Abstract

In this work, the antimalarial activity of two series of 20 and 7 synthetic 1,2,4-trioxanes and a set of 20 cyclic peroxy ketals are tested for correlation search by means of Molecular Quantum Similarity Measures (MQSM). QSAR models, dealing with different biological responses (IC90, IC50 and ED90) of the parasite Plasmodium Falciparum, are constructed using MQSM as molecular descriptors and are satisfactorily correlated. The statistical results of the 20 1,2,4-trioxanes are deeply analyzed to elucidate the relevant structural features in the biological activity, revealing the importance of phenyl substitutions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. T.D.R. News (News from the WHO Division of Control of Tropical Diseases), 46 (1994) 5.

  2. The Malaria Foundation International website, at http://www.malaria.org.

  3. Bruce-Chwatt, L.J. (Ed.), Chemotherapy of Malaria, 2nd ed., W.H.O., Geneva, 1981.

    Google Scholar 

  4. Klayman, D.L., Science, 228 (1985) 1049.

    Google Scholar 

  5. Butler, A.R. and Wu, Y.L., Chem. Soc. Rev., 21 (1992) 85.

    Google Scholar 

  6. Shen, C.C. and Zhuang, L.G., Med. Res. Rev., 4 (1984) 47.

    Google Scholar 

  7. Jefford, C.W., Velarde, J.A., Bernadinelli, G., Bray, D.H., Warhust, D.C. and Milhous, W.K., Helv. Chim. Acta, 76 (1993) 2775.

    Google Scholar 

  8. Jefford, C.W., Wang, Y. and Bernadinelli, G., Helv. Chim. Acta, 71 (1988) 2042.

    Google Scholar 

  9. Testa, B., Kyburz, E., Fuhrer, W. and Giger, R. (Eds.) Perspectives in Medicinal Chemistry, Vol. 25, VCH Publishers, Amsterdam, 1992, pp. 459-472.

    Google Scholar 

  10. Carbó, R., Arnau, J. and Leyda, L., Int. J. Quantum Chem., 17 (1980) 1185.

    Google Scholar 

  11. Carbó-Dorca, R. and Besalú, E., TEOCHEM, 451 (1998) 11.

    Google Scholar 

  12. Carbó-Dorca, R. and Mezey, P.G. (Eds.) Advances in Molecular Similarity, Vol. 2, JAI Press, Greenwich, CT, 1998, pp. 1-42.

    Google Scholar 

  13. Carbó-Dorca, R. and Mezey, P.G. (Eds.) Advances in Molecular Similarity, Vol. 2, JAI Press, Greenwich, CT, 1998, pp. 43-72.

    Google Scholar 

  14. Besalú, E., Carbó, R., Mestres, J. and Solà, M., Top. Curr. Chem., 173 (1995) 31.

    Google Scholar 

  15. Carbó, R. (Ed.) Molecular Similarity and Reactivity: From Quantum Chemical to Phenomenological Approaches, Kluwer, Amsterdam, 1995, pp. 3-30.

    Google Scholar 

  16. Carbó-Dorca, R. and Mezey, P.G. (Eds.) Advances in Molecular Similarity, Vol. 1, JAI Press, Greenwich, CT, 1996, pp. 1-42.

    Google Scholar 

  17. Carbó, R., Besalú, E., Amat, L. and Fradera, X., J. Math. Chem., 18 (1995) 237.

    Google Scholar 

  18. Fradera, X., Amat, L., Besalú, E. and Carbó-Dorca, R., Quant. Struct.-Act. Relat., 16 (1997) 25.

    Google Scholar 

  19. Lobato, M., Amat, L. and Carbó-Dorca, R., Quant. Struct.-Act. Relat., 16 (1997) 465.

    Google Scholar 

  20. Amat, L., Robert, D., Besalú, E. and Carbó-Dorca, R., J. Chem. Inf. Comput. Sci., 38 (1998) 624.

    Google Scholar 

  21. Robert, D., Amat, L. and Carbó-Dorca, R., J. Chem. Inf. Comput. Sci., 39 (1999) 333.

    Google Scholar 

  22. Robert, D., Gironés, X. and Carbó-Dorca, R., J. Comput. Aid. Mol. Des., 13 (1999) 597.

    Google Scholar 

  23. Gironés, X., Amat, L. and Robert, D. and Carbó-Dorca, R. J. Comput. Aid. Mol. Des., 14 (2000) 477.

    Google Scholar 

  24. Gironés, X., Gallegos, A. and Carbó-Dorca, R. J. Chem. Inf. Comput. Sci., 40 (2000) 1400.

    Google Scholar 

  25. Robert, D. and Carbó-Dorca, R., SAR QSAR Environ. Res., 10 (1999) 401.

    Google Scholar 

  26. Gironés, X., Amat, L. and Carbó-Dorca, R., SAR QSAR Environ. Res., 10 (1999) 545.

    Google Scholar 

  27. Carbó-Dorca, R., Robert, D., Amat, L., Gironés, X. And Besalú, E. (Ed.), Molecular Quantum Similarity and Drug Design, Springer, Lecture Notes in Chemistry 73, Berlin, 2000.

  28. Gironés, X., Robert, D. and Carbó-Dorca, R., J. Comp. Chem., 22 (2001) 255. An operative version can be obtained upon request at quantum@iqc.udg.es.

    Google Scholar 

  29. Constants, P. and Carbó, R., J. Chem. Inf. Comput. Sci., 35 (1995) 1046.

    Google Scholar 

  30. Amat, L. and Carbó-Dorca, R., J. Comput. Chem., 18 (1997) 2023.

    Google Scholar 

  31. Amat, L. and Carbó-Dorca, R., J. Comput. Chem., 20 (1999)

  32. Fitting ASA parameters form an assorted collection of basis sets can be downloaded from our web site: http://iqc.udg.es/cat/similarity/ASA/basisset.html.

  33. Cox, T.F. and Cox, M.A.A. (Eds), Multidimensional Scaling, Chapman & Hall, London, 1994.

    Google Scholar 

  34. Cuadras, C.M. and Arenas, C.A., Commun. Stat. Theor. Method., 19 (1990) 2261.

    Google Scholar 

  35. Allen, D.M., Technometrics, 16 (1974) 125.

    Google Scholar 

  36. See for example this detailed tutorial by Geladi, P. and Kowalsky, B.R. Anal. Chim. Acta, 185 (1986) 1.

    Google Scholar 

  37. Van der Waterbeemd, H. (Ed.), Chemometric Methods in Molecular Design, VCH, New York, 1995, pp. 309-318.

    Google Scholar 

  38. PC Spartan Pro, version 1.4, 1997, Wavefunction Inc, Irvine.

  39. Grigorov, M., Weber, J., Tronchet, J.M.J., Jefford, C.W., Milhous, W.K. and Maric, D., J. Chem. Inf. Comput. Sci., 37 (1997) 124.

    Google Scholar 

  40. Posner, G.H., O'Dowd, H., Ploypradith, P., Cumming J.N., Xie, S. and Shapiro, T.A., J. Med. Chem., 41 (1998) 2164.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Computational Chemistry, University of Girona, Campus Montilivi, 17071, Girona, Catalonia, Spain

    X. Gironés, A. Gallegos & R. Carbó-Dorca

Authors
  1. X. Gironés
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Gallegos
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Carbó-Dorca
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gironés, X., Gallegos, A. & Carbó-Dorca, R. Antimalarial activity of synthetic 1,2,4-trioxanes and cyclic peroxy ketals, a quantum similarity study. J Comput Aided Mol Des 15, 1053–1063 (2001). https://doi.org/10.1023/A:1015917510236

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1015917510236

Search

Navigation