Skip to main content
SpringerLink
Log in

Kinetic analysis of the hydroxyl mechanism of the antimalarial effect of fluorinated artemisinin derivatives

  • Published:
Kinetics and Catalysis Aims and scope Submit manuscript

Abstract

Kinetic schemes of intramolecular oxidation are constructed for 13 derivatives of 10-dihydroartemisinin containing fluorine substituents (F and CF3). Each step of the kinetic scheme is characterized by its enthalpy. The activation energy and rate constant of each step are calculated using the intersecting parabolas model. The competition between mono- and bimolecular radical reactions is taken into account. In the case of H abstraction from the α-hydroperoxy-C-H bond, the fragmentation of the molecule with the formation of hydroxyl radicals concerted with the abstraction is taken into account. The antimalarial efficiency of each drug due to the hydroxyl radicals only is calculated from the empirical dependence of the antimalarial activity IC50 on the number of hydroxyl radicals n OH generated by the compound. The compounds whose antimalarial activity is additionally caused by other factors are revealed.

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. Li, Y., Huang, H., and Wu, Y.-L., in Medicinal Chemistry of Bioactive Natural Products, Liang, X.-T. and Fang, W.-S., Eds., Hoboken, N.J.: Wiley, 2006, p. 183.

  2. Denisov, E.T., Solodova, S.L., and Denisova, T.G., Russ. Chem. Rev., 2010, vol. 79, p. 981.

    Article  CAS  Google Scholar 

  3. Meshnick, S.R., Taylor, T.E., and Kamchonwongpaisan, S., Microbiol. Rev., 1996, vol. 60, no. 2, p. 301.

    CAS  Google Scholar 

  4. Berman, P.A. and Adams, P.A., Free Radical Biol. Med., 1997, vol. 22, p. 1283.

    Article  CAS  Google Scholar 

  5. Meunier, B. and Robert, A., Acc. Chem. Res., 2010, vol. 43, p. 1444.

    Article  CAS  Google Scholar 

  6. Creek, D.J., Charman, W.N., Chiu, F.C.K., Prankerd, R.J., McCullough, K.J., Dong, Y., Vennerstrom, J.L., and Charman, S.A., J. Pharm. Sci., 2007, vol. 96, p. 2945.

    Article  CAS  Google Scholar 

  7. Avery, M.A., Gao, F., Chong, W.K.M., Hendrickson, T.F., Inman, W.D., and Crews, P., Tetrahedron, 1994, vol. 50, p. 957.

    Article  CAS  Google Scholar 

  8. Posner, G.H., Wang, D., Cumming, J.N., Oh, C.H., French, A.N., Bodley, A.L., and Shapiro, T.A., J. Med. Chem., 1995, vol. 38, p. 2273.

    Article  CAS  Google Scholar 

  9. Solodova, S.L., Denisov, E.T., and Denisova, T.G., Mendeleev Commun., 2008, vol. 18, no. 1, p. 24.

    Article  CAS  Google Scholar 

  10. Solodova, S.L. and Denisov, E.T., Russ. Chem. Bull., 2008, vol. 57, p. 274.

    Article  CAS  Google Scholar 

  11. Solodova, S.L. and Denisov, E.T., Russ. Chem. Bull., 2009, vol. 58, p. 777.

    Article  CAS  Google Scholar 

  12. Denisov, E.T. and Denisova, T.G., Russ. Chem. Bull., 2010, vol. 59, p. 1881.

    Article  CAS  Google Scholar 

  13. Denisov, E.T. and Denisova, T.G., Butlerov. Soobshch., 2010, vol. 23, no. 15, p. 11.

    Google Scholar 

  14. Denisov, E., Org. Biomol. Chem., 2011, vol. 9, no. 11, p. 4219.

    Article  CAS  Google Scholar 

  15. Denisov, E.T. and Denisova, T.G., Russ. Chem. Bull., 2011, vol. 60, p. 1421.

    Article  CAS  Google Scholar 

  16. Hindley, S., Ward, S.A., Storr, R.C., Searle, N.L., Bray, S.P., Park, B.R., Davies, J., and O’Neil, P.M., J. Med. Chem., 2002, vol. 45, p. 1053.

    Article  Google Scholar 

  17. Pacorel, B., Leung, S.C., Stachulski, A.V., Davies, J., Vivas, L., Lander, H., Ward, S.A., Kaiser, M., Brun, R., and O’Neil, P.M., J. Med. Chem., 2010, vol. 53, p. 633.

    Article  CAS  Google Scholar 

  18. Oidwai, T., Yadav, D.K., Khan, F., Dhawan, S., and Bhakuni, R.S., Current Pharm. Des., 2012, vol. 18, p. 6133.

    Article  Google Scholar 

  19. Posner, G.H., Parker, M.H., and Nortrop, J., J. Med. Chem., 1999, vol. 42, p. 300.

    Article  CAS  Google Scholar 

  20. Avery, M.A., Mureleedharan, K.M., Desai, P.V., Bandyopadhyaya, A.K., Furtado, M.M., and Tekwani, B.L., J. Med. Chem., 2003, vol. 46, p. 4244.

    Article  CAS  Google Scholar 

  21. Denisov, E.T., Denisova, T.G., and Pokidova, T.S., Handbook of Free Radical Initiators, Hoboken, N.J.: Wiley, 2003.

    Book  Google Scholar 

  22. Denisova, T.G. and Denisov, E.T., Pet. Chem., 2004, vol. 44, p. 250.

    Google Scholar 

  23. Denisov, E.T. and Tumanov, V.E., Russ. Chem. Rev., 2005, vol. 74, p. 825.

    Article  CAS  Google Scholar 

  24. Luo, Y.R., Handbook of Bond Dissociation Energies in Organic Compounds, Boca Raton, Fla.: CRC, 2003.

    Google Scholar 

  25. Denisov, E.T., Russ. Chem. Bull., 2013, vol. 62, p. 1533.

    Article  CAS  Google Scholar 

  26. Denisov, E.T., Kinet. Catal., 1995, vol. 36, no. 3, p. 345.

    CAS  Google Scholar 

  27. Denisov, E.T., in General Aspects of the Chemistry of Radicals, Alfassi, Z.B, Ed., Chichester: Wiley, 1999, p. 79.

  28. Denisov, E.T. and Afanas’ev, I.B., Oxidation and Antioxidants in Organic Chemistry and Biology, Boca Raton, Fla.: CRC, Taylor and Francis Group, 2005.

    Book  Google Scholar 

  29. Denisov, E.T. and Denisova, T.G., Russ. Chem. Rev., 2004, vol. 73, p. 1091.

    Article  CAS  Google Scholar 

  30. Denisova, T.G. and Denisov, E.T., Kinet. Catal., 2006, vol. 47, no. 1, p. 121.

    Article  CAS  Google Scholar 

  31. Denisov, E., Chatgilialoglu, C., Shestakov, A., and Denisova, T., Int. J. Chem. Kinet., 2009, vol. 41, p. 284.

    Article  CAS  Google Scholar 

  32. Aleksandrov, I.V., Teor. Eksp. Khim., 1976, vol. 12, no. 3, p. 299.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Problems of Chemical Physics, Russian Academy of Sciences, Chernogolovka, Moscow oblast, 142432, Russia

    E. T. Denisov & T. G. Denisova

Authors
  1. E. T. Denisov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. G. Denisova
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E. T. Denisov.

Additional information

Original Russian Text © E.T. Denisov, T.G. Denisova, 2015, published in Kinetika i Kataliz, 2015, Vol. 56, No. 3, pp. 286–300.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Denisov, E.T., Denisova, T.G. Kinetic analysis of the hydroxyl mechanism of the antimalarial effect of fluorinated artemisinin derivatives. Kinet Catal 56, 285–299 (2015). https://doi.org/10.1134/S0023158415030040

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0023158415030040

Keywords

Search

Navigation