Journal of Molecular Modeling

, Volume 16, Issue 12, pp 1919–1929

Modeling the binding modes of stilbene analogs to cyclooxygenase-2: a molecular docking study

  • Souhila Bouaziz-Terrachet
  • Amel Toumi-Maouche
  • Boubekeur Maouche
  • Safia Taïri-Kellou
Original Paper

Abstract

Stilbene analogs are a new class of anti-inflammatory compounds that effectively inhibit COX-2, which is the major target in the treatment of inflammation and pain. In this study, docking simulations were conducted using AutoDock 4 software that focused on the binding of this class of compounds to COX-2 protein. Our aim was to better understand the structural and chemical features responsible for the recognition mechanism of these compounds, and to explore their binding modes of interaction at the active site by comparing them with COX-2 co-crystallized with SC-558. The docking results allowed us to provide a plausible explanation for the different binding affinities observed experimentally. These results show that important conserved residues, in particular Arg513, Phe518, Trp387, Leu352, Leu531 and Arg120, could be essential for the binding of the ligands to COX-2 protein. The quality of the docking model was estimated based on the binding energies of the studied compounds. A good correlation was obtained between experimental logAr values and the predicted binding energies of the studied compounds.

Figure

The interaction of thirty stilbene analogs to COX-2 protein was studied using the automated docking simulation. The results of this study showed that the analogs can adopt two different binding modes in the active site of the COX-2 protein and that their predicted binding energies are in agreement with their experimental logAr values.

Keywords

Cyclooxygenase-2 COX-2 Molecular docking AutoDock Stilbenes NSAIDs Hydrophobic interactions 

References

  1. 1.
    Smith WL, DeWitt DL, Garavito RM (2000) Annu Rev Biochem 69:145–182CrossRefGoogle Scholar
  2. 2.
    Smith WL, DeWitt DL (1996) Adv Immunol 62:167–215CrossRefGoogle Scholar
  3. 3.
    Marnett LJ, Rowlinson SW, Goodwin DC, Kalgutkar AS, Lanzo CA (1999) J Biol Chem 274(33):22903–22906CrossRefGoogle Scholar
  4. 4.
    Picot D, Loll PJ, Garavito RM (1994) Nature 367:243–249CrossRefGoogle Scholar
  5. 5.
    Luong C, Miller A, Barnett J, Chow J, Ramesha C, Browner MF (1996) Nat Struct Biol 3:927–933CrossRefGoogle Scholar
  6. 6.
    Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildehaus D, Miyashiro JM, Penning TD, Seibert K, Isakson PC, Stallings WC (1996) Nature 384:644–648CrossRefGoogle Scholar
  7. 7.
    Zhang V, O’Sullivan M, Hussain H, Roswit WT, Holtzman MJ (1996) Biochem Biophys Res Commun 227:499–506CrossRefGoogle Scholar
  8. 8.
    Sirois J, Richards JS (1993) J Biol Chem 268:21931–21938Google Scholar
  9. 9.
    Yamagata K, Andreasson KI, Kaufmann WE, Barnes CA, Worley PF (1993) Neuron 11:371–386CrossRefGoogle Scholar
  10. 10.
    Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Perkins W, Lee L, Isakson P (1994) Proc Natl Acad Sci USA 91:12013–12017CrossRefGoogle Scholar
  11. 11.
    Turini ME, DuBois RN (2002) Ann Rev Med 53:35–57CrossRefGoogle Scholar
  12. 12.
    Singh R, Kumar R, Singh DP (2009) J Med Food 12(1):208–218CrossRefGoogle Scholar
  13. 13.
    Prasit P, Wang Z, Brideau C, Chan CC, Charleson S, Cromlish W, Ethier D, Evans JF, Ford–Hutchinson AW, Gauthier JY, Gordon R, Guay J, Gresser M, Kargman S, Kennedy B, Leblanc Y, Léger S, Mancini J, O’Neill GP, Ouellet M, Percival MD, Perrier H, Riendeau D, Rodger I, Tagari P, Thérien M, Vickers P, Wong E, Xu LJ, Young RN, Zambouni R (1999) Bioorg Med Chem Lett 9:1773–1778CrossRefGoogle Scholar
  14. 14.
    Li S, Zheng Y (2006) Int J Mol Sci 7:220–229CrossRefGoogle Scholar
  15. 15.
    Biava M, Porretta GC, Cappelli A, Vomero S, Manetti F, Botta M, Sautebin L, Rossi A, Makovec F, Anzini M (2005) J Med Chem 48:3428–3432CrossRefGoogle Scholar
  16. 16.
    Bosch J, Roca T, Catena JL, Llorens O, Pérez JJ, Lagunas C, Fernàndez AG, Miquel I, Fernàndez-Serrat A, Farrerons C (2000) Bioorg Med Chem Lett 10:1745–1748CrossRefGoogle Scholar
  17. 17.
    FitzGerald GA (2004) N Engl J Med 351:1709–1911CrossRefGoogle Scholar
  18. 18.
    Solomon DH, Schneeweiss S, Glynn RJ, Kiyota Y, Levin R, Mogun H, Avorn J (2004) Circulation 109:2068–2073CrossRefGoogle Scholar
  19. 19.
    Finckh A, Aronson MD (2005) Ann Intern Med 142:212–214Google Scholar
  20. 20.
    Dogné JM, Supuran CT, Pratico D (2005) J Med Chem 48:2251–2257CrossRefGoogle Scholar
  21. 21.
    Chavatte P, Yous S, Marot C, Baurin N, Lesieur D (2001) J Med Chem 44:3223–3230CrossRefGoogle Scholar
  22. 22.
    Desiraju GR, Gopalkrishnan B, Jetti RK, Nagaraju A, Raveendra D, Sarma JA, Sobhia ME, Thilagavathi R (2002) J Med Chem 45:4847–4857CrossRefGoogle Scholar
  23. 23.
    Liu H, Huang X, Shen J, Luo X, Li M, Xiong B, Chen G, Shen J, Yang Y, Jiang H, Chen K (2002) J Med Chem 45:4816–4827CrossRefGoogle Scholar
  24. 24.
    Soliva R, Almansa C, Kalko SG, Luque FJ, Orozco M (2003) J Med Chem 46:1372–1382CrossRefGoogle Scholar
  25. 25.
    Garg R, Kurup A, Mekapati SB, Hansch C (2003) Chem Rev 103:703–732CrossRefGoogle Scholar
  26. 26.
    Murias M, Handler N, Erker T, Pleban K, Ecker G, Saiko P, Szekeres T, Jäger W (2004) Bioorg Med Chem 12:5571–5578CrossRefGoogle Scholar
  27. 27.
    Baurin N, Mozziconacci JC, Arnoult E, Chavatte P, Marot C, Morin-Allory L (2004) J Chem Inf Comput Sci 44:276–285Google Scholar
  28. 28.
    Chen YC, Chen KT (2007) Acta Pharmacol Sin 12:2027–2032CrossRefGoogle Scholar
  29. 29.
    Dilber SP, Dobric SLJ, Juranic ZD, Markovic BD, Vladimirov SM, Juranic IO (2008) Molecules 13:603–615CrossRefGoogle Scholar
  30. 30.
    Ermondi G, Caron G, Lawrence R, Longo D (2004) J Comput Aided Mol Des 18:683–696CrossRefGoogle Scholar
  31. 31.
    Uddin MJ, Praveen Rao PN, Knaus EE (2005) Bioorg Med Chem 13:417–424CrossRefGoogle Scholar
  32. 32.
    Uddin MJ, Rao PN, Knaus EE (2004) Bioorg Med Chem Lett 14:1953–1956CrossRefGoogle Scholar
  33. 33.
    Uddin MJ, Rao PN, Knaus EE (2004) Bioorg Med Chem 12:5929–5940CrossRefGoogle Scholar
  34. 34.
    Moreau A, Chen QH, Praveen Rao PN, Knaus EE (2006) Bioorg Med Chem 14:7716–7727CrossRefGoogle Scholar
  35. 35.
    MDL Information Systems (2002) ISIS/Draw 2.5. MDL Information Systems, San LeandroGoogle Scholar
  36. 36.
    Cambridge Scientific Computing (2003) ChemOffice Ultra. Cambridge Scientific Computing, CambridgeGoogle Scholar
  37. 37.
    Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) J Comput Chem 25(13):1605–1612CrossRefGoogle Scholar
  38. 38.
    Sanner MF (1999) J Mol Graphics Mod 17:57–61Google Scholar
  39. 39.
    Morris Garrett M, Goodsell David S, Halliday Robert S, Huey R, Hart WE, Belew RK, Olson AJ (1998) J Comput Chem 19:1639–1662CrossRefGoogle Scholar
  40. 40.
    Solis FJ, Wets RJB (1981) Math Operations Res 6:19–30CrossRefGoogle Scholar
  41. 41.
    Greig GM, Francis DA, Falgueyret JP, Ouellet M, Percival MD, Roy P, Bayly C, Mancini JA, O’Neill GP (1997) Mol Pharmacol 52:829–838Google Scholar
  42. 42.
    Rao PN, Uddin MJ, Knaus EE (2004) J Med Chem 47:3972–3990CrossRefGoogle Scholar
  43. 43.
    Zebardast T, Zarghi A, Daraie B, Hedayati M, Dadrass OG (2009) Bioorg Med Chem Lett 19:3162–3165CrossRefGoogle Scholar
  44. 44.
    Kozak KR, Prusakiewicz JJ, Rowlinson SW, Schneider C, Marnett LJ (2001) J Biol Chem 276:30072–30077CrossRefGoogle Scholar
  45. 45.
    Selinsky BS, Gupta K, Sharkey CT, Loll PJ (2001) Biochemistry 40:5172–5180CrossRefGoogle Scholar
  46. 46.
    Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ (2003) J Biol Chem 278:45763–45769CrossRefGoogle Scholar
  47. 47.
    Kiefer JR, Pawlitz JL, Moreland KT, Stegeman RA, Hood WF, Gierse JK, Stevens AM, Goodwin DC, Rowlinson SW, Marnett LJ, Stallings WC, Kurumbail RG (2000) Nature 405:97–101CrossRefGoogle Scholar
  48. 48.
    Teague SJ (2003) Nat Rev Drug Discov 2:527–541CrossRefGoogle Scholar
  49. 49.
    Gunasekaran K, Nussinov R (2007) J Mol Biol 365:257–273CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Souhila Bouaziz-Terrachet
    • 1
  • Amel Toumi-Maouche
    • 1
  • Boubekeur Maouche
    • 1
  • Safia Taïri-Kellou
    • 1
  1. 1.Laboratoire de Physico-Chimie Théorique et Chimie Informatique, Faculté de ChimieAlgerAlgeria

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