Biopolym. Cell. 2021; 37(3):177-184.
Bioorganic Chemistry
Identification of novel protein kinase CK2 inhibitors among indazole derivatives
1Vdovin V. S., 1Lukashov S. S., 1Borysenko I. P., 1Borovykov O. V., 1Protopopov M. V., 1Bdzhola V. G., 1Yarmoluk S. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143


Aim. To synthesize the novel purine bioisosteres – indazole derivatives and evaluate inhibitory activity of these compounds towards CK2 in the in vitro system. Methods. Chemical synthesis, 1H and 13C NMR spectroscopy, LC-MS method, determination of residual enzyme activity using ATP consumption tests with a luciferase Kinase-Glo® luminescent kinase assay. Results. Known synthetic methods of indazole chemistry were originally applied to the synthesis of 3-aryl-indazole-7-carboxylic acids. Conditions of cross-coupling of 3-bromo-indazole derivatives with arylboronic acids were substantially improved. 3-aryl-indazole 5- and 7-carboxylic acids have shown IC50 in a range 3.1–6.5 μM in luciferase luminescent kinase assay. Conclusions. The synthesis of 3-aryl-indazole-7-carboxylic acids has been developed. Novel inhibitors of the protein kinase CK2 among indazole derivatives have been identified among the 3-aryl-indazole 5- and 7-carboxylic acids. It has been shown the crucial impact of carboxyl group on the inhibitory activity of studied compounds.
Keywords: Indazole, chemical synthesis, luciferase luminescent kinase assay, protein kinase inhibitor, protein kinase CK2


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