Russian Journal of General Chemistry

, Volume 87, Issue 12, pp 3029–3035 | Cite as

Design, Synthesis, and Biological Evaluation of 1,4-Bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes as Potential Chk1 Inhibitors

Letters to the Editor
  • 3 Downloads

Abstract

A series of 1,4-bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes were designed as inhibitors of checkpoint kinase 1 (Chk1), based on the structure‒activity relationships for known inhibitors through docking simulations. The docking results suggested that the title compounds were similar to known inhibitors in interaction with the catalytic site of Chk1. Twelve compounds were synthesized by a one-pot procedure from amines, dimethyl acetylenedicarboxylate, and glyoxal in water in the presence of catalytic amounts of γ-cyclodextrin. The inhibitory activities of the synthesized compounds were evaluated in vitro using EC9706 esophageal cancer cells. The results indicated that 1,4-bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes significantly inhibited Chk1 (IC50 10.45 μM).

Keywords

Chk1 inhibitors 1,4-bis(2,3-dihydro-5-oxopyrrol-4-yl)-1,3-butadienes synthesis biological testing 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kastan, M.B. and Bartek, J., Nature, 2004, vol. 432, p. 316.CrossRefGoogle Scholar
  2. 2.
    Dai, Y. and Grant, S., Clin. Cancer Res., 2010, vol. 16, p. 376.CrossRefGoogle Scholar
  3. 3.
    Chen, J.S., Lin, S.Y., Tso, W.L., Yeh, G.C., Lee, W.S., Tseng, H., Chen, L.C., and Ho, Y.S., Mol. Carcinogen, 2006, vol. 45, p. 461.CrossRefGoogle Scholar
  4. 4.
    Carrassa, L., Broggini, M., Erba, E., and Damia, G., Cell Cycle, 2004, vol. 3, p. 1175.CrossRefGoogle Scholar
  5. 5.
    Ling, H., Wen, L., Ji, X., Tang, Y., He, J., Tan, H., Xia, H., Zhou, J., and Su, Q., Braz. J. Med. Biol. Res., 2010, vol. 43, p. 271.CrossRefGoogle Scholar
  6. 6.
    Ambre, P.K., Pissurlenkar, R.R., Coutinho, E.C., and Iyer, R.P., Canadian J. Chem., 2012, vol. 90, p. 675.CrossRefGoogle Scholar
  7. 7.
    King, C., Diaz, H., Barnard, D., Barda, D., Clawson, D., Blosser, W., Cox, K., Guo, S., and Marshall, M., Invest. New Drug, 2014, vol. 32, p. 213.CrossRefGoogle Scholar
  8. 8.
    Dai, Y., Chen, S., Kmieciak, M., Zhou, L., Lin, H., Pei, X.-Y., and Grant, S., Mol. Cancer Therap., 2013, vol. 12, p. 878.CrossRefGoogle Scholar
  9. 9.
    Archie, N.T., Rendahl, K.G., Sheikh, T., Cheema, H., Aardalen, K., Embry, M., Ma, S., Moler, E.J., Ni, Z.J., and de Menezes, D.E.L, Clin. Cancer Res., 2007, vol. 13, p. 591.CrossRefGoogle Scholar
  10. 10.
    Eldebss, T.M., Gomha, S.M., Abdulla, M.M., and Arafa, R.K., Med. Chem. Commun., 2015, vol. 6, p. 852.CrossRefGoogle Scholar
  11. 11.
    Smaill, J.B., Lee, H.H., Palmer, B.D., Thompson, A.M., Squire, C.J., Baker, E.N., Booth, R.J., Kraker, A., Hook, K., and Denny, W.A., Bioorg. Med. Chem. Lett., 2008, vol. 18, p. 929.CrossRefGoogle Scholar
  12. 12.
    Zhao, B., Bower, M.J., McDevitt, P.J., Zhao, H., Davis, S.T., Johanson, K.O., Green, S.M., Concha, N.O., and Zhou, B.-B.S., J. Biol. Chem., 2002, vol. 277, p. 46609.CrossRefGoogle Scholar
  13. 13.
    Jackson, J.R., Gilmartin, A., Imburgia, C., Winkler, J.D., Marshall, L.A., and Roshak, A., Cancer Res., 2000, vol. 60, p. 566.Google Scholar
  14. 14.
    Gojo, I., Perl, A., Luger, S., Baer, M.R., Norsworthy, K.J., Bauer, K.S., Tidwell, M., Fleckinger, S., Carroll, M., and Sausville, E.A., Invest. New Drug, 2013, vol. 31, p. 1217.CrossRefGoogle Scholar
  15. 15.
    Kumar, R. and Lown, J.W., Eur. J. Med. Chem., 2005, vol. 40, p. 641.CrossRefGoogle Scholar
  16. 16.
    Van Heerden, L., Cloete, T.T., Breytenbach, J.W., de Kock, C., Smith, P.J., Breytenbach, J.C., and N’Da, D.D., Eur. J. Med. Chem., 2012, vol. 55, p. 335.CrossRefGoogle Scholar
  17. 17.
    Liu, Q., Song, X.-Q., and Yan, H., Acta Crystallograph. C, 2014, vol. 70, p. 965.CrossRefGoogle Scholar
  18. 18.
    Ma, Y.-C., Su, N., Shi, X.-J., Zhao, W., Ke, Y., Zi, X., Zhao, N.-M., Qin, Y.-H., Zhao, H.-W., and Liu, H.-M., Toxicol. Appl. Pharm., 2015, vol. 282, p. 227.CrossRefGoogle Scholar
  19. 19.
    Jackson, J.-R., Gilmartin, A., and Imburgia, C., Cancer Res., 2000, vol. 60, p. 566.Google Scholar
  20. 20.
    Sun, M.M., Sun, Y.S., Zhao, Z.H., and Zhang, M.Z., Zhonghua Shiyan Waike Zazhi, 2014, vol. 31, p. 1128.Google Scholar
  21. 21.
    Morris, G.M., Goodsell, D.S., and Halliday, R.S., J. Comput. Chem., 1998, vol. 19, p 1639.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2017

Authors and Affiliations

  1. 1.College of Life Science and BioengineeringBeijing University of TechnologyBeijingChina

Personalised recommendations