Journal of Structural Chemistry

, Volume 59, Issue 7, pp 1564–1571 | Cite as

3D QSAR Studies on Benzyl Phenyl Ether Diamidine Derivatives with Antiprotozoal Activities

  • J. TongEmail author
  • Y. Wu
  • M. Bai


Human African trypanosomiasis (HAT) is a neglected tropical disease, and some drugs treating HAT have been used for even more than 60 years. Currently, a series of benzyl phenyl ether diamidine derivatives are discovered, which exhibit high antiprotozoal activities and low cytotoxicity, leading to good development prospects. The comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA) are used to study the relationship between the structure and antiprotozoal activities. The established 3D QSAR model shows not only significant statistical quality, but also satisfies predictive ability: the best CoMFA model had r2 = 0.958 and q2 = 0.766, the best CoMSIA model had r2 = 0.957 and q2 = 0.812, the predictive ability of CoMFA and CoMSIA model were further confirmed by a test set which had 11 compounds, giving the correlation coefficient Qext2 of 0.792, 0.873, respectively. The contour maps and contribution maps show important features that can improve the antiprotozoal activity: position 3 from substituent R4 should be a low electronegativity group, position 4 from substituent R4 should have higher electronegativity, substituent R2 should be selected to a low electronegativity and small bulk group. Together these results may offer some useful theoretical information in designing potential inhibitors.


benzyl phenyl ether derivatives human African trypanosomiasis Trypanosoma brucei rhodesiense 3D QSAR 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. Keating, J. O. Yukich, C. S. Sutherland, et al. Acta Trop., 2015, 150,4.CrossRefGoogle Scholar
  2. 2.
    J. Stephanie Migchelsen, Philippe Büscher, et al. Int. J. Infect. Dis., 2011, 15(8),517.CrossRefGoogle Scholar
  3. 3.
    P. S. Pere, C. Giuliano, P. Massimo, et al. Int. J. Health Geographics, 2010, 9(1),9.CrossRefGoogle Scholar
  4. 4.
    B. Reto, B. Johannes, C. Francois, et al. Lancet, 2010, 375,148.CrossRefGoogle Scholar
  5. 5.
    P. P. Simarro, J. Franco, A. Diarra, et al. Parasitology, 2012, 139(7),842.CrossRefGoogle Scholar
  6. 6.
    J. Pépin and F. Milord Adv. Parasitol., 1994, 33(33),1.Google Scholar
  7. 7.
    P. Gerardo, K. Serena, M. Wilfried, et al. Lancet, 2009, 374(9683),7.CrossRefGoogle Scholar
  8. 8.
    T. J. Robert, N. Bakela, A. W. Stephen, et al. PLOS Neglected Trop. Dis., 2011, 5(6), 1151.CrossRefGoogle Scholar
  9. 9.
    T. Els, B. T. Bernadette, T. David, et al. PLOS Neglected Trop. Dis. 2010, 4(7),923.Google Scholar
  10. 10.
    J. A. Vicente, K. Marcel, and D. Christophe. Bioorg. Med. Chem. Lett., 2012, 22(14), 4506.CrossRefGoogle Scholar
  11. 11.
    Y. X. Zhao, Q. Wang, Q. Q. Meng, et al. Bioorg. Med. Chem., 2012, 20(3), 1240.CrossRefGoogle Scholar
  12. 12.
    A. P. Donald, A. B. Stanislav, M. B. Svetlana, et al. Eur. J. Med. Chem., 2013, 67(17),310.Google Scholar
  13. 13.
    D. C. Richard, E. P. David, and D. B. Jeffrey. J. Med. Chem., 1988, 110, 5959.Google Scholar
  14. 14.
    D. C. Richard, D. B. Jeffrey, and E. P. David. Quant. Struct.-Act. Relat., 1988, 7,18.CrossRefGoogle Scholar
  15. 15.
    K. Gerhard and A. Ute. J. Comput.-Aided Mol. Des., 1999, 13(1),1.CrossRefGoogle Scholar
  16. 16.
    S. Horrick, X. L. Cheng, and K. B. John. J. Chem. Inf. Model., 2012, 52(2),515.CrossRefGoogle Scholar
  17. 17.
    S. Y. Liao, L. Qian, T. F. Miao, et al. Eur. J. Med. Chem., 2009, 44(7), 2822.CrossRefGoogle Scholar
  18. 18.
    S. K. Shridhar, R. P. Maulik, and T. T. Tanaji. Bioorg. Med. Chem., 2008, 16, 3675.CrossRefGoogle Scholar
  19. 19.
    SYBYL 8.1, Tripos 1699 South Hanley Road., St. Louis., Missouri, 63144.Google Scholar
  20. 20.
    G. Johann and M. Mario. Tetrahedron, 1980, 36(22), 3219.CrossRefGoogle Scholar
  21. 21.
    V. N. Viswanadhan, A. K. Ghose, G. R. Revankar, et al. J. Med. Chem., 1991, 34(2),526.CrossRefGoogle Scholar
  22. 22.
    P. Geladi and S. Wold. Chemom. Intell. Lab. Syst., 1987, 2(4), 273.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.College of Chemistry and Chemical EngineeringShaanxi University of Science and TechnologyXi′anP. R. China

Personalised recommendations