title: Docking and 3D-QSAR studies of 7-hydroxycoumarin derivatives as CK2 inhibitors.
abstract: 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 CK2alpha. 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 (q2=0.694, r2=0.916, N (no. of components)=7, r2(pred)=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 CK2alpha amino acids provide useful hints for new inhibitors design.
authors.affiliation: College of Life Science and Bioengineering, Beijing University of Technology, Beijing 100124, China. nanatonglei@bjut.edu.cn
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Rugang
authors.initials: R
authors.lastname: Zhong
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002867:Chromones / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D004642:Emodin / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D014468:Umbelliferones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
chemical_list: C528849:3,8-dibromo-7-hydroxy-4-methylchromen-2-one; D002867:Chromones; D008024:Ligands; D047428:Protein Kinase Inhibitors; D014468:Umbelliferones; C031477:7-hydroxycoumarin; D047390:Casein Kinase II; D004642:Emodin