Assessment of structural peculiarities of glaziovianin A interaction with human α-, β and γ-tubulins

  • P. A. Karpov
  • S. I. Spivak
  • O. V. Rayevsky
  • O. Yu. Nyporko
  • S. P. Ozheredov
  • Ya. B. Blume
DOI: https://doi.org/10.7124/FEEO.v22.972

Abstract

Aim. To determine the features of the ligand-protein interaction of glaziovianin A and human α-, β- and γ-tubulin. Methods. Protein and ligand spatial structure modelling (I-Tasser, Grid), molecular docking (CCDC Gold), molecular dynamics simulation (GROMACS). Results. Using the method of molecular docking in CCDC Gold ligand-protein complexes of glaziovianin A and human α-, β- and γ-tubulin were reconstructed. Studied ligand interactions in GTP/GDP-exchange and colchicine binding sites of different tubulin isotypes. The built ligand-protein complexes were studied using molecular dynamics simulations. Conclusions. Binding of glaziovianin A with human tubulin was confirmed exposing its derivatives as perspective tubulin effectors. The binding energies of ligand-protein interaction confirm higher affinity for β-tubulin molecules, and it was suggested that glazovianin A binding may occur at two alternative sites: GTP/GDP-exchange site and site of colchicine binding.

Keywords: tubulin, glaziovianin A, binding, antitumor activity.

References

Hait W.N. Anticancer drug development: the grand challenges. Nat. Rev. Drug Discov. 2010. Vol. 9. P. 253–254. doi: 10.1038/nrd3144

Faucette S., Wagh S., Trivedi A., Venkatakrishnan K., Gupta N. Reverse translation of US Food and Drug Administration reviews of oncology new molecular entities approved in 2011–2017: Lessons learned for anticancer drug development. Clin. Transl. Sci. 2017. doi: 10.1111/cts.12527.

Griffin R., Ramirez R.A. Molecular targets in non-small cell lung cancer. Ochsner J. 2017. Vol. 17. P. 388–392.

Pasquier E., Kavallaris M. Microtubules: A dynamic target in cancer therapy. IUBMB Life, 2008. Vol. 60 (3). P. 165–170. doi: 10.1002/iub.25

Karpov P.A., Bryrsun V.M., Rayevsky A.V., Demchuk O.M., Pydiura N.O., Ozheredov S.P., Samofalova D.A., Spivak S.I., Yemets A.I., Kalchenko V.I., Blume Ya.B. High-throughput screening of new antimitotic compounds based on potential of virtual organization CSLabGrid. Nauka innov. 2015. Vol. 11. P. 92–100. doi: 10.15407/scin11.01.092

Cao Y.N., Zheng L.L., Wang D., Liang X.X., Gao F., Zhou X.L. Recent advances in microtubule-stabilizing agents. Eur. J. Med. Chem. 2018. Vol. 143. P. 806–828. doi: 10.1016/j.ejmech.2017.11.062

Yokosuka A., Haraguchi M., Usui T., Kazami S., Osada H., Yamori T., Mimaki Y. Glaziovianin A, a new isoflavone, from the leaves of Ateleia glazioviana and its cytotoxic activity against human cancer cells. Bioorg. Med. Chem. Lett. 2007. Vol. 17. P. 3091–3094. doi: 10.1016/j.bmcl.2007.03.044

Kobayashi M., Natsume T., Tamaoki S., Watanabe J., Asano H., Mikami T., Miyasaka K., Miyazaki K., Gondo M., Sakakibara K., Tsukagoshi S. Antitumor activity of TZT-1027, a novel dolastatin 10 derivative. Jpn. J. Cancer Res. 1997. Vol. 88. P. 316–327. doi: 10.1111/j.1349-7006.1997.tb00383.x

Dixon R.A., Pasinetti G.M. Flavonoids and isoflavonoids: from plant biology to agriculture and neuroscience. Plant Physiology. 2010. Vol. 154. P. 453–457. doi: 10.1104/pp.110.161430

Torres F.C., García-Rubiño M.E., Lozano-López C., Kawano D.F., Eifler-Lima V.L., von Poser G.L., Campos J.M. Imidazoles and benzimidazoles as tubulin-modulators for anti-cancer therapy. Curr. Med. Chem. 2015. Vol. 22. P. 1312–1323. doi: 10.2174/0929867322666150114164032