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

Protein kinase CK2 is a highly pleiotropic protein capable of phosphorylating hundreds substrates. It involved in numerous cellular functions, including cell viability, apoptosis, proliferation and survival, angiogenesis, or ER-stress response. As activity found perturbed many pathological states, cancers, it becomes an attractive target for the pharma. A large number low-mass ATP-competitive inhibitors have already been developed, majority them halogenated. We tested binding six series halogenated heterocyclic ligands derived from commercially available 4,5-dihalo-benzene-1,2-diamines. These ligand were selected to enable separation scaffold effect hydrophobic interactions attributed directly presence halogen atoms. In silico molecular docking was initially applied test capability each at ATP-binding site CK2. HPLC-derived hydrophobicity data are compared with affinity assessed by low-volume differential scanning fluorimetry (nanoDSF). identified three promising scaffolds, two which not yet described as but may lead potent inhibitors. The inhibitory against CK2α toxicity four reference lines determined eight compounds most nanoDSF assay.