Mykhailo V Mahdysiuk, Galyna P Volynets, Volodymyr G Bdzhola, Oleksandr A Bieda, Sergiy S Lukashov, Vladislav M Sapelkin, Leonid L Karbovskyi, Sergiy M Yarmoluk
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Discovery of new aurone derivatives as submicromolar CK2 inhibitors.
Protein kinase CK2 is a promising therapeutic target, and this study explores 54 aurone derivatives as potential CK2 inhibitors. Activity was evaluated using luminescent and capillary electrophoresis assays, identifying 17 compounds with submicromolar activity. The most potent inhibitors shared key structural features: a benzo group on the A-ring, a hydrogen bond acceptor at the R4' position, and an additional substituent at the R3' position of the B-ring. Molecular docking revealed similar binding modes among active compounds, with interactions involving Leu45, Val53, Val66, Met163, Phe113, Lys68, and Ile174. Notably, BFO25 showed the highest activity (IC50 = 3 nM at 100 μM ATP). These findings highlight aurones as promising CK2 inhibitors and emphasise the significance of specific structural features.
期刊介绍：
Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents.
Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research.
The journal’s focus includes current developments in:
Enzymology;
Cell biology;
Chemical biology;
Microbiology;
Physiology;
Pharmacology leading to drug design;
Molecular recognition processes;
Distribution and metabolism of biologically active compounds.
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