title: Evaluation of 3-carboxy-4(1H)-quinolones as inhibitors of human protein kinase CK2.
abstract: Due to the emerging role of protein kinase CK2 as a molecule that participates not only in the development of some cancers but also in viral infections and inflammatory failures, small organic inhibitors of CK2, besides application in scientific research, may have therapeutic significance. In this paper, we present a new class of CK2 inhibitors-3-carboxy-4(1H)-quinolones. This class of inhibitors has been selected via receptor-based virtual screening of the Otava compound library. It was revealed that the most active compounds, 5,6,8-trichloro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (7) (IC(50) = 0.3 microM) and 4-oxo-1,4-dihydrobenzo[h]quinoline-3-carboxylic acid (9) (IC(50) = 1 microM), are ATP competitive (K(i) values are 0.06 and 0.28 microM, respectively). Evaluation of the inhibitors on seven protein kinases shows considerable selectivity toward CK2. According to theoretical calculations and experimental data, a structural model describing the key features of 3-carboxy-4(1H)-quinolones responsible for tight binding to CK2 active site has been developed.
authors.affiliation: Institute of Molecular Biology and Genetics of National Academy of Sciences of Ukraine, 150 Zabolotny str., Kyiv 03143, Ukraine.
authors.forename: Andriy G
authors.initials: AG
authors.lastname: Golub
authors.forename: Olexander Ya
authors.initials: OY
authors.lastname: Yakovenko
authors.forename: Volodymyr G
authors.initials: VG
authors.lastname: Bdzhola
authors.forename: Vladislav M
authors.initials: VM
authors.lastname: Sapelkin
authors.forename: Piotr
authors.initials: P
authors.lastname: Zien
authors.forename: Sergiy M
authors.initials: SM
authors.lastname: Yarmoluk
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D047390:Casein Kinase II / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D008024:Ligands; D008958:Models, Molecular; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D011955:Receptors, Drug / Q000737:chemistry / Q000235:genetics; D011994:Recombinant Proteins; D012984:Software; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D008024:Ligands; D015363:Quinolones; D011955:Receptors, Drug; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D047390:Casein Kinase II