title: Discovery and characterization of synthetic 4'-hydroxyflavones-New CK2 inhibitors from flavone family.
abstract: Human protein kinase CK2 is one of the most intriguing enzymes, which functional role still remains unclear despite of decades of studying. At present there is abundant evidence pointing to the fact that inhibitors of CK2 could be used as pharmaceutical agents to treat cancer, viral infections and inflammatory diseases. Here we report novel synthetic flavone inhibitors, 4'-hydroxyflavones, possessing high activity towards CK2. These compounds were identified with receptor-based virtual screening and then chemically optimized on the base of rationale derived from biochemical screening and molecular modeling. It has been demonstrated that synthetic flavone derivatives are much more potent CK2 inhibitors than the natural ones, and we believe that their further examination will be helpful for studying biological role of CK2 as well as for development of new kinase-oriented drugs.
authors.affiliation: Otava Ltd, 65 Ellerslie Ave., Suite 560, Toronto, Ontario M2N 1Y1, Canada.
authors.forename: Andriy G
authors.initials: AG
authors.lastname: Golub
authors.forename: Volodymyr G
authors.initials: VG
authors.lastname: Bdzhola
authors.forename: Olga V
authors.initials: OV
authors.lastname: Ostrynska
authors.forename: Iaroslav V
authors.initials: IV
authors.lastname: Kyshenia
authors.forename: Vladislav M
authors.initials: VM
authors.lastname: Sapelkin
authors.forename: Andriy O
authors.initials: AO
authors.lastname: Prykhod'ko
authors.forename: Olexander P
authors.initials: OP
authors.lastname: Kukharenko
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Yarmoluk
mesh_terms: D001665:Binding Sites; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D047309:Flavones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D062105:Molecular Docking Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D047309:Flavones; D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D047390:Casein Kinase II; C043562:flavone
keywords: 4′-Hydroxyflavone; Docking; Drug design; Inhibitor; Molecular modeling; Protein kinase CK2