Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Docking and Quantum Mechanics-Guided CoMFA Analysis of b-RAF Inhibitors

  • Muddassar, M. (Korea Institute of Science and Technology) ;
  • Pasha, F. A. (Korea Institute of Science and Technology) ;
  • Yoo, Kyung-Ho (Korea Institute of Science and Technology) ;
  • Lee, So-Ha (Korea Institute of Science and Technology) ;
  • Cho, Seung-Joo (Research Center for Resistant Cells, Chosun University)
  • Published : 2008.08.20
Download PDF
⟨ Previous Next ⟩

Abstract

Pyrazine derivatives bind to b-RAF receptor which is important in cancer therapy. The ligand-receptor interactions have been studied by comparative molecular field analysis (CoMFA) and molecular docking methods. Applying conventional ligand-based alignment schemes for the whole set was not successful. However, QM and DFT results suggested that some ligands have electrostatic interaction while others have steric interactions. On the basis of these results, we divided the dataset into two subsets. Electrostatic effect was found to be important in one set while steric effect for the other. Best docking modes were obtained for each subset based on the available crystal structure. These receptor-guided CoMFA models propose an interesting possibility which is difficult to obtain otherwise. i.e., in one binding mode the electrostatic interaction plays a key role for one subset ($q^2$ = 0.46, $r^2$ = 0.98), while in another binding mode steric effect is important with another subset ($q^2$ = 0.43, $r^2$ = 0.74).

Keywords

References

  1. Ikawa, S.; Fukui, M.; Ueyama, Y.; Tamaoki, N.; Yamamoto, T.; Toyoshima, K. Mol. Cell Biol. 1988, 8, 2651-2654 https://doi.org/10.1128/MCB.8.6.2651
  2. Sridhar, S. S.; Hedley, D.; Siu, L. L. Mol. Cancer Ther. 2005, 4, 677-685 https://doi.org/10.1158/1535-7163.MCT-04-0297
  3. Malumbres, M.; Carnero, A. Prog. Cell Cycle Res. 2003, 5, 5-18
  4. Davies, H.; Bignell, G. R.; Cox, C.; Stephens, P.; Edkins, S.; Clegg, S.; Teague, J.; Woffendin, H.; Garnett, M. J.; Bottomley, W.; Davis, N.; Dicks, E.; Ewing, R.; Floyd, Y.; Gray, K.; Hall, S.; Hawes, R.; Hughes, J.; Kosmidou, V.; Menzies, A.; Mould, C.; Parker, A.; Stevens, C.; Watt, S.; Hooper, S.; Wilson, R.; Jayatilake, H.; Gusterson, B. A.; Cooper, C.; Shipley, J.; Hargrave, D.; Pritchard- Jones, K.; Maitland, N.; Chenevix-Trench, G.; Riggins, G. J.; Bigner, D. D.; Palmieri, G.; Cossu, A.; Flanagan, A.; Nicholson, A.; Ho, J. W.; Leung, S. Y.; Yuen, S. T.; Weber, B. L.; Seigler, H. F.; Darrow, T. L.; Paterson, H.; Marais, R.; Marshall, C. J.; Wooster, R.; Stratton, M. R.; Futreal, P. A. Nature 2002, 417, 949-954 https://doi.org/10.1038/nature00766
  5. Tuveson, D. A.; Weber, B. L.; Herlyn, M. Cancer Cell 2003, 4, 95-98 https://doi.org/10.1016/S1535-6108(03)00189-2
  6. Niculescu-Duvaz, I.; Roman, E.; Whittaker, S. R.; Friedlos, F.; Kirk, R.; Scanlon, I. J.; Davies, L. C.; Niculescu-Duvaz, D.; Marais, R.; Springer, C. J. J. Med. Chem. 2006, 49, 407-416 https://doi.org/10.1021/jm050983g
  7. Brose, M. S.; Volpe, P.; Feldman, M.; Kumar, M.; Rishi, I.; Gerrero, R.; Einhorn, E.; Herlyn, M.; Minna, J.; Nicholson, A.; Roth, J. A.; Albelda, S. M.; Davies, H.; Cox, C.; Brignell, G.; Stephens, P.; Futreal, P. A.; Wooster, R.; Stratton, M. R.; Weber, B. L. Cancer Res. 2002, 62, 6997-7000
  8. Xu, X.; Quiros, R. M.; Gattuso, P.; Ain, K. B.; Prinz, R. A. Cancer Res. 2003, 63, 4561-4567
  9. Morrison, D. K. Nature 2004, 428, 813-815
  10. Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. J. Mol. Biol. 1996, 261, 470-489 https://doi.org/10.1006/jmbi.1996.0477
  11. Lowinger, T. B.; Riedl, B.; Dumas, J.; Smith, R. A. Curr. Pharm. Des. 2002, 8, 2269-2278 https://doi.org/10.2174/1381612023393125
  12. Khire, U. R.; Bankston, D.; Barbosa, J.; Brittelli, D. R.; Caringal, Y.; Carlson, R.; Dumas, J.; Gane, T.; Heald, S. L.; Hibner, B.; Johnson, J. S.; Katz, M. E.; Kennure, N.; Kingery-Wood, J.; Lee, W.; Liu, X. G.; Lowinger, T. B.; McAlexander, I.; Monahan, M. K.; Natero, R.; Renick, J.; Riedl, B.; Rong, H.; Sibley, R. N.; Smith, R. A.; Wolanin, D. Bioorg. Med. Chem. Lett. 2004, 14, 783-786 https://doi.org/10.1016/j.bmcl.2003.11.041
  13. Lackey, K.; Cory, M.; Davis, R.; Frye, S. V.; Harris, P. A.; Hunter, R. N.; Jung, D. K.; McDonald, O. B.; McNutt, R. W.; Peel, M. R.; Rutkowske, R. D.; Veal, J. M.; Wood, E. R. Bioorg. Med. Chem. Lett. 2000, 10, 223-226 https://doi.org/10.1016/S0960-894X(99)00668-X
  14. Hall-Jackson, C. A.; Eyers, P. A.; Cohen, P.; Goedert, M.; Boyle, F. T.; Hewitt, N.; Plant, H.; Hedge, P. Chem. Biol. 1999, 6, 559-568 https://doi.org/10.1016/S1074-5521(99)80088-X
  15. Thaimattam, R.; Daga, P.; Rajjak, S. A.; Banerjee, R.; Iqbal, J. Bioorg. Med. Chem. 2004, 12, 6415-6425 https://doi.org/10.1016/j.bmc.2004.09.029
  16. Pasha, F. A.; Srivastava, H. K.; Singh, P. P. Bioorg. Med. Chem. 2005, 13, 6823-6829 https://doi.org/10.1016/j.bmc.2005.07.064
  17. Pasha, F. A.; Srivastava, H. K.; Singh, P. P. Mol. Divers 2005, 9, 215-220 https://doi.org/10.1007/s11030-005-2711-x
  18. Ashek, A.; Cho, S. J. Bioorg. Med. Chem. 2006, 14, 1474-1482 https://doi.org/10.1016/j.bmc.2005.10.001
  19. Ashek, A.; Lee, C.; Park, H.; Cho, S. J. Chemosphere 2006, 65, 521-529 https://doi.org/10.1016/j.chemosphere.2006.01.010
  20. Pasha, F. A.; Muddassar, M.; Jung, H.; Yang, B.- S.; Lee, C.; Oh, J. S.; Cho, S. J.; Cho, H. Bull. Korean Chem. Soc. 2008, 29(3), 647 https://doi.org/10.5012/bkcs.2008.29.3.647
  21. San Juan, A. A.; Cho, S. J.; Cho, H. Bull. Korean Chem. Soc. 2006, 27(10), 1531 https://doi.org/10.5012/bkcs.2006.27.10.1531
  22. Clark, M.; Cramer, R. D.; Vanopdenbosch, N. Journal of Computational Chemistry 1989, 10, 982-1012 https://doi.org/10.1002/jcc.540100804
  23. Cramer, R. D.; Patterson, D. E.; Bunce, J. D. J. Am. Chem. Soc. 1988, 110, 5959-5967 https://doi.org/10.1021/ja00226a005
  24. Parr, R. G.; Pearson, R. G. J. Am. Chem. Soc. 1983, 105, 7512-7516 https://doi.org/10.1021/ja00364a005
  25. Iczkowski, R.; Margrave, J. L. J. Am. Chem. Soc. 1961, 83, 3547-3549 https://doi.org/10.1021/ja01478a001
  26. Parr, R. G.; Von Szentpaly, L.; Liu, S. B. J. Am. Chem. Soc. 1999, 121, 1922-1924 https://doi.org/10.1021/ja983494x

Cited by

  1. Pharmacophore model generation and 3D-QSAR analysis of N-acyl and N-aroylpyrazolines for enzymatic and cellular B-Raf kinase inhibition vol.22, pp.5, 2013, https://doi.org/10.1007/s00044-012-0210-z
  2. Pharmacophore Identification and Validation Study of CK2 Inhibitors Using CoMFA/CoMSIA vol.74, pp.2, 2009, https://doi.org/10.1111/j.1747-0285.2009.00841.x
  3. Structural studies of B-type Aurora kinase inhibitors using computational methods vol.31, pp.2, 2010, https://doi.org/10.1038/aps.2009.188