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Article

Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2

Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland
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Academic Editor: Pascal Marchand
Molecules 2021, 26(11), 3163; https://doi.org/10.3390/molecules26113163
Received: 27 February 2021 / Revised: 18 May 2021 / Accepted: 22 May 2021 / Published: 25 May 2021
(This article belongs to the Special Issue Kinase Inhibitors 2021)
Protein kinase CK2 is a highly pleiotropic protein kinase capable of phosphorylating hundreds of protein substrates. It is involved in numerous cellular functions, including cell viability, apoptosis, cell proliferation and survival, angiogenesis, or ER-stress response. As CK2 activity is found perturbed in many pathological states, including cancers, it becomes an attractive target for the pharma. A large number of low-mass ATP-competitive inhibitors have already been developed, the majority of them halogenated. We tested the binding of six series of halogenated heterocyclic ligands derived from the commercially available 4,5-dihalo-benzene-1,2-diamines. These ligand series were selected to enable the separation of the scaffold effect from the hydrophobic interactions attributed directly to the presence of halogen atoms. In silico molecular docking was initially applied to test the capability of each ligand for binding at the ATP-binding site of CK2. HPLC-derived ligand hydrophobicity data are compared with the binding affinity assessed by low-volume differential scanning fluorimetry (nanoDSF). We identified three promising ligand scaffolds, two of which have not yet been described as CK2 inhibitors but may lead to potent CK2 kinase inhibitors. The inhibitory activity against CK2α and toxicity against four reference cell lines have been determined for eight compounds identified as the most promising in nanoDSF assay. View Full-Text
Keywords: kinase CK2; differential scanning fluorimetry; molecular modeling; halogenated heterocycles; hydrophobic contribution; ligand binding; inhibitory activity; cell toxicity kinase CK2; differential scanning fluorimetry; molecular modeling; halogenated heterocycles; hydrophobic contribution; ligand binding; inhibitory activity; cell toxicity
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MDPI and ACS Style

Winiewska-Szajewska, M.; Maciejewska, A.M.; Speina, E.; Poznański, J.; Paprocki, D. Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2. Molecules 2021, 26, 3163. https://doi.org/10.3390/molecules26113163

AMA Style

Winiewska-Szajewska M, Maciejewska AM, Speina E, Poznański J, Paprocki D. Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2. Molecules. 2021; 26(11):3163. https://doi.org/10.3390/molecules26113163

Chicago/Turabian Style

Winiewska-Szajewska, Maria, Agnieszka M. Maciejewska, Elżbieta Speina, Jarosław Poznański, and Daniel Paprocki. 2021. "Synthesis of Novel Halogenated Heterocycles Based on o-Phenylenediamine and Their Interactions with the Catalytic Subunit of Protein Kinase CK2" Molecules 26, no. 11: 3163. https://doi.org/10.3390/molecules26113163

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