Docking and 3D-QSAR studies of 7-hydroxycoumarin derivatives as CK2 inhibitors

Protein kinase CK2 is involved in a broad range of physiological events. 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC) analogues show favorable inhibitory activity targeting CK2 alpha. Two methods were used to build 3D-QSAR models for DBC derivatives. The ligand-based (LB) studies were performed based on the lower energy conformations employing atom fit alignment rule. The receptor-based (RB) models were also derived using bioactive conformations. Contour maps of RB CoMSIA model (q(2) = 0.694, r(2) = 0.916, N (no. of components) = 7, r(pred)(2) = 0.87) including the steric, electronic, hydrophobic and hydrogen bond acceptor fields were employed to explain factors affecting activities of inhibitors. The good consistency between the contour maps and the properties of CK2 alpha amino acids provide useful hints for new inhibitors design. Crown Copyright (C) 2009 Published by Elsevier Masson SAS. All rights reserved.