Pharmaceutical Chemistry Journal

, Volume 45, Issue 9, pp 539–546 | Cite as

Structure–property relationships in series of natural and synthetic inhibitors of catalytic activity of 15-lipoxygenase

  • V. R. Khairullina
  • A. Ya. Gerchikov
  • I. A. Taipov
  • H. Boegel
  • F. S. Zarudii

Structural signatures characteristic of high-, medium-, and low-efficiency inhibitors of the catalytic activity of 15-lipoxygenase (15-LOG) have been revealed using the SARD-21 (Structure Activity Relationship & Design) computer system. The degree of their influence on the efficiency of the inhibiting activity was estimated. Based on these data, two models are constructed for predicting the interval of LOG-inhibiting activity of various sulfur-, nitrogen-, and oxygen-containing heterocyclic compounds with an 80% prediction accuracy level for the two recognition methods. The revealed structural features can be used to construct highly selective inhibitors of 15-LOG catalytic activity.


inhibitor structure—property relationship catalytic activity 


  1. 1.
    E. T. Denisov and I. B. Afanas?ev, Oxidation and Antioxidants in Organic Chemistry and Biology, Taylor & Francis, Boca Raton (2005).Google Scholar
  2. 2.
    A. R. Brash, J. Biol. Chem., 274, 23679–23682 (1999).Google Scholar
  3. 3.
    K. Miyazawa, Y. Iimori, and M. Makino, Jpn. J. Pharmacol., 38, 199–205 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    E. I. Solomon, J. Zhou, F. Neese, and E. G. Pavel, Chem. Biol., 4, 795–808 (1997).PubMedCrossRefGoogle Scholar
  5. 5.
    E. Pontiki and D. Hadjipavlou-Litina, Curr. Enzyme Inhib., 1, 309–327 (2005).CrossRefGoogle Scholar
  6. 6.
    A. B. Camargo, R. W. Masuelli, and J. L. Burba, Acta Hortic., 688, 309–312 (2005).Google Scholar
  7. 7.
    H. Tapiero, D. Townsend, and K. Tew, Biomed. Pharmacother., 58, 183–193 (2004).PubMedCrossRefGoogle Scholar
  8. 8.
    U. Sing, B. Prithiviraj, B. Sarma, et al., Ind. J. Exp. Bid. Indian., 39, 310–322 (2001).Google Scholar
  9. 9.
    E. Block, R. Iyer, S. Grisoni, et al., J. Am. Chem. Soc., 110, 7813–7827 (1988).CrossRefGoogle Scholar
  10. 10.
    S. T. Prigge, J. S. Boyington, M. Faig, and K. S. Doctor, Biochimie, 79, 629–636 (1997).PubMedCrossRefGoogle Scholar
  11. 11.
    L. A. Tyurina, O. V. Tyurina, and A. M. Kolbin, Methods and Results of Design and Prediction of Biologically Active Compounds [in Russian], Gilem, Ufa (2007).Google Scholar
  12. 12.
    Y. Vasques-Martinez, R. V. Ohri, V. Kenyon, and T. R. Holman, Bioorg. Med. Chem., 15, 7408–7425 (2007).CrossRefGoogle Scholar
  13. 13.
    A. B. Camargo and E. Marchevsky, J. Agric. Food Chem., 55, 3096–3103 (2007).CrossRefGoogle Scholar
  14. 14.
    D. S. Weinstein, W. Liu, K. Ngu, et al., Bioorg. Med. Chem. Lett., 17, 5115–5120 (2007).PubMedCrossRefGoogle Scholar
  15. 15.
    D. S. Weinstein,W. Liu, Z. Gu, et al., Bioorg. Med. Chem. Lett., 15, 1435–1440 (2005).PubMedCrossRefGoogle Scholar
  16. 16.
    P. N. Rao, Q. H. Chen, and E. E. Knaus, J. Med. Chem., 49, 1668–1683 (2006).Google Scholar
  17. 17.
    U. P. Kelavkar, W. Glasgow, S. J. Olson, et al., Neoplasia, 6, 821–830 (2004).PubMedGoogle Scholar
  18. 18.
    R. J. Hsieh, J. B. German, and J. E. Kinsella, Lipids, 23, 322–326 (1988).PubMedCrossRefGoogle Scholar
  19. 19.
    G. D. Jones, L. Russell, V. M. Darley-Usmar, D. Stone, and M. T. Wilson, Biochemistry, 35, 7197–7203 (1996).PubMedCrossRefGoogle Scholar
  20. 20.
    O. Werz, B. Szellas, and D. Steinhilber, Eur. J. Biochem., 267, 1263–1269 (2000).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2011

Authors and Affiliations

  • V. R. Khairullina
    • 1
  • A. Ya. Gerchikov
    • 1
  • I. A. Taipov
    • 1
  • H. Boegel
    • 2
  • F. S. Zarudii
    • 3
  1. 1.Bashkir State UniversityUfaRussia
  2. 2.Martin Luther University of Halle-WittenbergHalleGermany
  3. 3.Bashkir State Medical UniversityUfaRussia

Personalised recommendations