Molecular docking of 1,3-oxazole derivatives into the active site of tubulin

1Semenyuta, IV
1Tanchuk, VYu.
1Lobko, EO
1Metelytsia, LO
1Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv
Dopov. Nac. akad. nauk Ukr. 2017, 1:103-108
Section: Biochemistry
Language: Ukrainian

The effect of 1,3-oxazole in the colchicine binding site (CBS) of β-tubulin is studied in silico, the molecular docking of 1,3-oxazole in the CBS of β-tubulin is performed, and the results of the analysis of ligand-receptor complexes are shown. An adequate model of the CBS of B-subunit of β-tubulin is created. The model is checked by the redocking of colchicine into the CBS, and the stable ligand-protein complex (Ebind = −8 kcal/mol, RMSD = 1.2042 Å) is obtained. The high cytotoxic activity of compounds 1, 3, and 4, which form a stable ligand-protein complexes (Ebind = −7.7, −5.5, −6.2, −5.8 kcal/mol), is justified by the molecular docking. It is shown that these compounds bind to amino acid residues of CBS via hydrogen bonds and π−σ bonds, like colchicine. Compounds 1, 3, and 4 can be recommended for the further study as promising antimitotic agents.

Keywords: 1, 3-oxazole derivatives, colchicine, molecular docking, tubulin
  1. Jordan M.A., Wilson L. Nat. Rev. Cancer., 2004, 4: 253—265.
  2. Bhattacharyya B., Panda D., Gupta S., Banerjee M. Med. Res. Rev., 2008, 1: 155-183.
  3. Kumar N. J. Biol. Chem., 1981, 20: 10435-10441.
  4. Lu Y., Chen J., Xiao M., Li W., Miller D. Pharm. Res., 2012, 11: 2943—2971.
  5. Semenyuta I.V., Kovalishin V.V., Kopernik I.N., Vasilenko A.N., Prokopenko V.V., Brovarets V.S. Reports of the National Academy of Sciences of Ukraine, 2013, 11: 168-173 (in Russian).
  6. Semenyuta I.V., Kovalishyn V.V., Pilyo S.G., Blagodatnyy V.N., Trokhimenko E.P., Brovarets V.S., Metelitsa L.A. Reports of the National Academy of Sciences of Ukraine, 2014, 12: 152—157 (in Russian).
  12. Trott O., Olson A.J. J. Comput. Chem., 2010, 31: 455-461.