Biopolym. Cell. 2026; 42(2):121-128.
https://doi.org/10.7124/bc.000B3C
Molecular and Cell Biotechnologies
2,4-Dianilino-pyrimidine derivatives as submicromolar CK2 inhibitors
1Mahdysiuk M. V., 1Volynets G. P., 1Tarnavskiy S. S., 1Bdzhola V. G., 1Lukashov S. S., 1Marchenko S. V., 1Antonenko S. V., 1Syniugin A. R., 1Yarmoluk S. M.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03143

Abstract

Aim. This study aims to identify and characterize new 2,4-dianilinopyrimidine derivatives as inhibitors of protein kinase CK2, a key enzyme implicated in numerous pathological processes. Methods. A series of newly synthesized 2,4-dianilinopyrimidine derivatives was evaluated using a luminescence-based assay to determine the inhibitory activity against CK2. Luminescence based structure-activity relationship analysis and molecular docking studies were performed to elucidate key interactions within the ATP-binding site. Results. Several compounds demonstrated submicromolar inhibitory activity against CK2 (IC50). SAR analysis and docking revealed that the position of the carboxylic group on the aniline ring is critical for activity. Compounds bearing an ortho-carboxyl group were active, whereas meta substitution led to a loss of activity, consistent with interactions between the carboxyl group and Lys68. Additionally, the presence of polar substituents on the second aniline ring contributed to activity, likely through interactions with the hinge region residues, including Val116, Asn117, and Asn118. Conclusions. The 2,4-dianilinopyrimidine scaffold represents a promising platform for the development of potent CK2 inhibitors, with key structural features identified for further optimization.
Keywords: enzyme inhibition, bis anilinopyrimidine, molecular docking, protein kinase, luminescence
Full text: (PDF, in English)

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