|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|
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|
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