Chemistry of Heterocyclic Compounds

, Volume 49, Issue 11, pp 1589–1598 | Cite as

Reactivity of Aziridine-2-Carboxamide (Leakadine) with Nucleophiles in Aqueous Solutions*

  • R. Aleksis
  • K. Jaudzems
  • J. Ivanova
  • R. Žalubovskis
  • I. Kalvinsh
  • E. LiepinshEmail author

We describe studies of aziridine-2-carboxamide (Leakadine) reactivity with N-, O-, and S-nucleophiles in aqueous solutions using NMR spectroscopy and chemical synthesis. The results show that nucleophilic ring opening reactions of Leakadine with N- and O-nucleophiles take place only in acidic solutions, while reactions with S-nucleophiles occur irrespective of the pH and at a significantly higher reaction rate. These data suggest that the antitumor and immunostimulating activity of Leakadine may be associated with inhibition of extracellular cysteine proteases of cancer cells.


aziridine-2-carboxamide Leakadine non-activated aziridines nucleophilic ring opening 


  1. 1.
    F. M. D. Ismail, D. O. Levitsky, and V. M. Dembitsky, Eur. J. Med. Chem., 44, 3373 (2009).CrossRefGoogle Scholar
  2. 2.
    S. A. Giller, M. J. Lidaka, E. J. Markava, and A. A. Zidermane, GB Pat. Appl. 1052711; Chem. Abstr., 66, 55483 (1966).Google Scholar
  3. 3.
    O. W. Burtner, L. C. Jensen, and J. M. Rumball, Ann. Intern. Med., 38, 1222 (1953).CrossRefGoogle Scholar
  4. 4.
    M. P. Sykes, D. A. Karnofsky, F. S. Philips, and J. H. Burchenal, Cancer, 6, 142 (1953).CrossRefGoogle Scholar
  5. 5.
    P. D. Lawley and P. Brookes, J. Mol. Biol., 25, 143 (1967).CrossRefGoogle Scholar
  6. 6.
    I. Y. Kalvinsh and E. B. Astapenok, Belg. Pat. Appl. 860239; Chem. Abstr., 90, 34103 (1979).Google Scholar
  7. 7.
    P. T. Trapentsier, I. Ya. Kalvin'sh, É. É. Liepin'sh, and É. Ya. Lukevits, Khim. Geterotsikl. Soedin., 350 (1983). [Chem. Heterocycl. Compd., 19, 283 (1983).]Google Scholar
  8. 8.
    P. T. Trapentsier, I. Ya. Kalvin'sh, É. É. Liepin'sh, and É. Lukevits, Khim. Geterotsikl. Soedin., 1227 (1983). [Chem. Heterocycl. Compd., 19, 982 (1983).].Google Scholar
  9. 9.
    U. Bicker, in: G. Mathe, and F. M. Muggia (editors), Recent Results in Cancer Research, Vol. 75, Heidelberg (1980), p. 147.Google Scholar
  10. 10.
    J. L. Wike-Hooley, J. Haveman, and J. S. Reinhold, Radiother. Oncol., 2, 343 (1984).CrossRefGoogle Scholar
  11. 11.
    M. Turks, I. Rijkure, S. Belyakov, D. Zicāne, V. Kumpiņš, Ē. Bizdēna, A. Meikas, and A. Valkna, Khim. Geterotsikl. Soedin., 928 (2012). [Chem. Heterocycl. Compd., 48, 861 (2012).]Google Scholar
  12. 12.
    T. Ingebrigtsen and T. Lejon, Tetrahedron Lett., 47, 3949 (2006).CrossRefGoogle Scholar
  13. 13.
    M. M. Mohamed and B. F. Sloane, Nat. Rev. Cancer, 6, 764 (2006).CrossRefGoogle Scholar
  14. 14.
    H.-H. Otto and T. Schirmeister, Chem. Rev., 97, 133 (1997).CrossRefGoogle Scholar
  15. 15.
    R. J. Abraham, The Analysis of High Resolution NMR Spectra, Elsevier Publishing Co. (1971), p. 302.Google Scholar
  16. 16.
    R. G. Kostyanovsky, P. E. Dormov, P. Trapencieris, B. Strumfs, G. K. Kadorkina, I. I. Chervin, and I. Ya. Kalvin’s, Mendeleev Commun., 9, 26 (1999).CrossRefGoogle Scholar
  17. 17.
    P. T. Trapentsier, I. Ya. Kalvin’sh, É. É. Liepin’sh, É. Ya. Lukevich, G. A. Bremanis, and A. V. Eremeev, Khim. Geterotsikl. Soedin., 774 (1985). [Chem. Heterocycl. Compd., 21, 646 (1985).]Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • R. Aleksis
    • 1
  • K. Jaudzems
    • 1
  • J. Ivanova
    • 1
  • R. Žalubovskis
    • 1
  • I. Kalvinsh
    • 1
  • E. Liepinsh
    • 1
    Email author
  1. 1.Latvian Institute of Organic SynthesisRigaLatvia

Personalised recommendations