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The Pharmaceutical Society of Korea (대한약학회)
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Comparison of Some 3-(Substituted-Benzylidene)-1, 3-Dihydro-Indolin Derivatives as Ligands of Tyrosine Kinase Based on Binding Mode Studies and Biological Assay

  • Olgen, Sureyya (Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ankara)
  • Published : 2006.11.30
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Abstract

A series of 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one, 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione and 2, 2'-dithiobis 3-(substituted-benylidene)-1, 3-dihydro-indole derivatives was investigated as inhibitor of $p60^{c-Src}$tyrosine kinase by performing receptor docking studies and inhibitory activity toward tyrosine phosphorylation. Some compounds were shown to be docked at the site, where the selective inhibitor PP1 [1-tert-Butyl-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidine-4-yl-amine] was embedded at the enzyme active site. Evaluation of all compounds for the interactions with the parameters of lowest binding energy levels, capability of hydrogen bond formations and superimposibility on enzyme active site by docking studies, it can be assumed that 3-(substituted-benzylidene)-1, 3-dihydro-indolin-2-one and thione derivatives have better interaction with enzyme active site then 2, 2'-dithiobis 3-(substituted-benzylidene)-1, 3-dihydro indole derivatives. The test results for the inhibitory activity against tyrosine kinase by Elisa method revealed that 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione derivatives have more activity then 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one derivatives.

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References

  1. Akaho, E., Fujikawa, C., Runion, H. I., Hill, C. R., and Nakaho, H., A study on docking mode of hiv protease and their inhibitors. J. Chem. Software, 5, 147 -162 (1999) https://doi.org/10.2477/jchemsoft.5.147
  2. Braud, E. M., Nourrisson, M. R., Tonnerre, A., Picot, C., LeBaut, G., Renard, P., Pfeiffer, B., and Tucker, G., Potential Inhibitors of angiogenesis. Part I: 3-(imidazolyl-4 (5)-ylmethylene) indolin-2-ones. J. Enzyme Inhib. Med. Chem., 18, 243-252 (2003) https://doi.org/10.1080/1475636031000106575
  3. Coda, A. C., Invernizzi, A. G., Righetti, P. P., and Tacconi, G., (Z)- and (E)-Arylindene-1,3-dihydro indol-2-ones: configuration, conformation, and infrared carbonyl stretching frequencies. J. Chem. Soc. Perkin Trans, 2, 615-619 (1984)
  4. Cortes-Funes, H., Antiangiogenic agents. Drugs of Today, 38, 11-19 (2002)
  5. Ewing T. J. A. and Kuntz, I. D., Critical evaluation of search algorithms for automated molecular docking and database screening. J. Comput. Chem., 18, 1175-1189 (1997) https://doi.org/10.1002/(SICI)1096-987X(19970715)18:9<1175::AID-JCC6>3.0.CO;2-O
  6. Ewing T. J. A., Makino, S., Skillman, A. G., and Kuntz, I. D., Dock 4.0: Search strategies for automated molecular docking flexible molecule databases. J. Comp.-Aid. Mol. Des., 15, 411-428 (2001) https://doi.org/10.1023/A:1011115820450
  7. Fabbro, D., Parkinson, D., and Matter, A., Protein tyrosine kinase inhibitors: new treatment modalities. Curr. Opin. Pharmacol. 2, 374-381 (2002) https://doi.org/10.1016/S1471-4892(02)00179-0
  8. Folkman, J., Anti-angiogenesis: new concepts for theraphy of solid tumors. Ann. Surg., 175, 409-416 (1972) https://doi.org/10.1097/00000658-197203000-00014
  9. Folkman, J., Tumor angiogenesis. Adv. Cancer Res., 43, 175- 203 (1985) https://doi.org/10.1016/S0065-230X(08)60946-X
  10. Fong, T. A. T., Shawver, L. K., App, H., Sun, L., Tang, C., Rice, A., Kim, Y. H., Schreck, R., Chen, J., Dowd, B., Suto, E., Vasile, S., Wang, X., Hirth, K. P., and McMahon, G., SU 5416: a potent and selective Flk-1/KDR kinase inhibitor that blocks Flk-1 phosphorylation, endotelhial cell mitogenesis, and tumor growth. Proc. Am. Assoc. Cancer Res., 39, 560-567 (1998)
  11. Fong, T. A. T., Shawer, L. K., Sun, L., Tang, C., App, H., Powell, T. J., Kim, Y. H., Schreck, R., Wang, X., Risau, W., Ullrich, A., Hirth, K. P., and McMahon, G., SU 5416: is a potent and selective inhibitor of the vascular endothelial growth factor receptor (Flk-1/KDR) that inhibits tyrosine kinase catalysis, tumor vascularization, and growth for multiple tumor types. J. Cancer Res., 59, 99-106 (1999)
  12. Hamby, J. M. and Showalter, H. D. H., Small molecule inhibitors of tumor promoted angiogenesis, including protein kinase inhibitors. Pharmacol. Ther., 82, 169-193 (1999) https://doi.org/10.1016/S0163-7258(98)00053-9
  13. Hanke, J. H., Gardner, J. P., Dow, R. L., Changelian, P. S., Brissette, W. H., Weringer, E. J., Pollok, B. A., and Connelly, P. A., Discovery of a novel, potent and src family selective tyrosine kinase inhibitor. J. Biol. Chem., 271, 695-701 (1996) https://doi.org/10.1074/jbc.271.2.695
  14. Khols, D. W. D., Fry, D. W., and Kraker, A. J., Inhibitors of tyrosine kinase. Curr. Opin. Oncol., 9, 562-568 (1997) https://doi.org/10.1097/00001622-199711000-00012
  15. Kuntz, I. D., Dock. 4.0 (University of California, San Francisco Web Site) (1998)
  16. Levitzki, A. and Grazit, A., Tyrosine kinase inhibition: an approach to drug development. Science, 267, 1782-1788 (1995) https://doi.org/10.1126/science.7892601
  17. Lyne, P. D., Structure-based virtual screening: an overview. Drug Discovery Today, 7, 1047-1055 (2002) https://doi.org/10.1016/S1359-6446(02)02483-2
  18. Meng, E. C., Scoichet, B. K., and Kuntz, I. D., Automated docking with grid-base evaluation. J. Comput. Chem., 13, 505-524 (1992) https://doi.org/10.1002/jcc.540130412
  19. Mohammadi, M., McMahon, G., Sun, L., Tang, C., Hirth, P., Yeh, B. K., Hubbard, S. R., and Schlessinger, J., Structures of the tyrosine kinase domain of fibroblast growth factor receptor in complex with inhibitors. Science, 276, 955-960 (1997) https://doi.org/10.1126/science.276.5314.955
  20. Noonberg, S. B. and Benz, C. C., Tyrosine kinase inhibitors targeted to the epidermal growth factor receptor subfamily. Drugs, 59, 753-767 (2000) https://doi.org/10.2165/00003495-200059040-00003
  21. Olgen, S., Akaho, E., and Nebioglu, D., Synthesis and antityrosine activity of 3-(substituted-benzylidene)-1, 3-dihydroindolin derivatives: investigation of their role against $p60^{c-Src}$ receptor tyrosine kinase with the application of receptor docking studies. Farmaco, 60, 497-506 (2005) https://doi.org/10.1016/j.farmac.2005.01.015
  22. Olgen, S., Akaho, E., and Nebioglu, D., Evaluation of indole esters as inhibitors of $p60^{c-Src}$ receptor tyrosine kinase and investigation of the inhibition using receptor docking studies. J. Enzy. Inhib. Med. Chem. 18, 485-490 (2003) https://doi.org/10.1080/14756360310001612211
  23. Rewcastle, G. W., Palmer, B. D., Dobrusin, E. M., Fry, D. W., Kraker, A. J., and Denny, W. A., Tyrosine kinase inhibitors. 3. Structure-activity relationships for inhibition of protein tyrosine kinases by nuclear-substituted derivatives of 2, 2'-dithiobis (1-methyl-N-phenyl-1H-indole-3-carboxamide). J. Med. Chem., 37, 2033-2042 (1994) https://doi.org/10.1021/jm00039a016
  24. Roussidis, A. E. and Karamanos, N. K., Inhibition of receptor tyrosine kinase-based signal transduction as specific target for cancer treatment. In vivo, 16, 459-470 (2002)
  25. Schulz-Gasch, T. and Stahl, M., Binding site characteristics in structure-based virtual screening: evaluation of current docking tools. J. Mol. Model., 9, 47-57 (2003) https://doi.org/10.1007/s00894-002-0112-y
  26. Sun, L., Tran, N., Tang, F., App, H., Hirth, P., McMahon, G., and Tang, C., Synthesis and biological evaluations of 3- substituted indolin-2-ones: a novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular tyrosine kinases. J. Med. Chem., 41, 2588-2603 (1998) https://doi.org/10.1021/jm980123i
  27. Sun, Y, Ewing T. J. A., Skillman, A. G., and Kuntz, I. D., CombiDOCK: Structure-based combinatorial docking and library design. J. Comp.-Aid. Mol. Des., 12, 597-604 (1998) https://doi.org/10.1023/A:1008036704754
  28. Sun, L., Tran, N., Liang, C., Tang, F., Rice, A., Schreck, R., Waltz, K., Shaever, L. K., McMahon, G., and Tang, C., Design, synthesis and evaluations of substituted 3-[(3- or 4- carboxy ethyl pyrrol-2-yl)methylindenyl]indolin-2-ones as inhibitors of VEGF, FGF and PDGF receptor tyrosine kinases. J. Med. Chem., 42, 5120-5130 (1999) https://doi.org/10.1021/jm9904295
  29. Sun, L., Tran, N., Liang, C., Hubbard, S., Tang, F., Lipson, K., Schreck, R., Zhou, Y., McMahon, G., and Tang, C., Identification of substituted 3-[(4, 5, 6, 7-Tetrahydro-1H-indole-2-yl) methylene]-1, 3-hydroindole-2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rb tyrosine kinases. J. Med. Chem., 43, 2655-2663 (2000) https://doi.org/10.1021/jm9906116
  30. Taylor, V. C., Buckley, C. D., Douglas, M., Cody, A. J., Simmons, D. L., and Freeman, S. D., The myeloid-specific sialic acid binding receptor, CD33, associated with the protein-tyrosine phosphatases, SHP-1 and SHP-2. J. Biol. Chem., 274, 11505-11512 (1999) https://doi.org/10.1074/jbc.274.17.11505
  31. Taylor, R. D., Jewsbury, P. J., and Essex, J. W., A review of protein-small molecule docking methods. J. Comp.-Aid. Mol. Des., 16, 151-166 (2002) https://doi.org/10.1023/A:1020155510718
  32. Terrence, R. B., Protein-tyrosine kinase inhibitors. Drugs of the Future, 17, 119-131 (1992)
  33. Thompson, A. M., Rewcastle, G. W., Boushelle, S. L., Hartl, B. G., Kraker, A. J., Lu, G. H., Batley, B. L., Panek, R. L., Showalter, H. D. H., and Denny, W. A., Synthesis and structure-activity relationships of 7-substituted 3-(2, 6-dichlorophenyl)-1, 6- naphthydrin-2 (1H)-ones as selective inhibitors of $p60^{c-Src}$. J. Med. Chem., 43, 3134-3147 (2000) https://doi.org/10.1021/jm000148t
  34. Traxler, P. and Lyndon, N., Recent advances in protein tyrosine kinase inhibitors. Drugs of the Future, 20, 1261-1274 (1995) https://doi.org/10.1358/dof.1995.020.12.330232
  35. Widler, L., Green, J., Missbach, M., Susa, M., and Altmann, E., 7-Alkyl- and 7-cycloalkyl-5-aryl-pyrrolo[2, 3-d]pyrimidinespotent inhibitors of the tyrosine kinase c-Src. Bioorg. Med. Chem. Lett., 11, 849-852 (2001) https://doi.org/10.1016/S0960-894X(01)00079-8
  36. Zhu, X., Kim, J. L., Newcomb, J. R., Rose, P. E., Stover, D. R., Toledo, L. M., Zhao, H., and Morgenstern, K. A., Structural Analysis of the Lymphocyte-Specific Kinase Lck in Complex with Non-Selective and Src Family Selective Kinase. Structure, 7, 651-661 (1999) https://doi.org/10.1016/S0969-2126(99)80086-0