Jornal Internacional de Desenvolvimento e Pesquisa de Drogas

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Abstrato

In Silico Design of Protein Kinase 2 Inhibitors Using Molecular Docking and Pharmacophore Modelling

Sara Hammad, Roza Meghnem, Dalila Meziane and Souhila Bouaziz-Terrachet

Flavonoids derivatives are a new class of natural substances that effectively inhibit CK2 protein. This protein represents an attractive pharmacological target for the treatment of cancer. With the aim to better understand the structural and chemical features responsible for the recognition mechanism of these compounds, and to explore their binding modes of interaction, a series of thirty-seven hydroxy flavones derivatives were docked into CK2 active site using FlexX software. The superposition of the docked conformation of the crystal ligand to that in the CK2 crystal structure are close since the RMSD between the two conformations was only 0.75 Å. The docking results show that important conserved residues, in particular Val116, Asp120, Arg47, Asn118, Ile66, Met163 and Val45, could be essential for the binding of the ligands to CK2 protein. The docking energies are in good agreement with the corresponding experimental activities PIC₅₀ values of studied compounds since a significant correlation coefficient (R=0.866) was obtained. Then, the obtained docking conformations of some active compounds were used to generate pharmacophore models with the help of Ligand Scout. Therefore, the information provided in this study can be useful for designing new CK2 based on flavonoids compounds.