title: Structure-based discovery of novel flavonol inhibitors of human protein kinase CK2.
abstract: Serine/threonine protein kinase CK2 controls vast variety of fundamental processes in cell life; however, despite long period of study, its functional role is not completely determined. CK2 has a significant pathogenic potential and its activity is strictly associated with the development of various kinds of disorders. There are a growing number of facts that inhibitors of CK2 could be used as pharmaceutical agents for the cancer treatment, viral infections, and inflammatory diseases. In this article, we report structural and biological data on the novel synthetic flavonol derivatives, 3-hydroxy-4'-carboxyflavones, possessing a high inhibitory activity toward CK2. With the aid of combinatorial organic synthesis, molecular modeling techniques and biochemical in vitro tests, we studied the structure-activity relationships of flavonol derivatives and developed binding model describing their key intermolecular interactions with the CK2 ATP-binding site. Obtained data show that the synthetic 3-hydroxy-4'-carboxyflavones possess the highest activity among flavonol inhibitors of CK2 known till date.
authors: Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotnogo Str., Kyiv 03143, Ukraine. andrew.golub@gmail.com
authors: Andriy G
authors: AG
authors: Golub
authors: Volodymyr G
authors: VG
authors: Bdzhola
authors: Yaroslav V
authors: YV
authors: Kyshenia
authors: Vladislav M
authors: VM
authors: Sapelkin
authors: Andriy O
authors: AO
authors: Prykhod'ko
authors: Olexander P
authors: OP
authors: Kukharenko
authors: Olga V
authors: OV
authors: Ostrynska
authors: Sergiy M
authors: SM
authors: Yarmoluk
mesh_terms: D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020134:Catalytic Domain; D055808:Drug Discovery; D044948:Flavonols / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity / Q000187:drug effects; D013816:Thermodynamics
chemical_list: D044948:Flavonols; D047428:Protein Kinase Inhibitors; D047390:Casein Kinase II