6478-80-4Relevant articles and documents
Synthesis of novel halogenated heterocycles based on o‐phenylenediamine and their interactions with the catalytic subunit of protein kinase ck2
Maciejewska, Agnieszka Monika,Paprocki, Daniel,Poznański, Jaros?aw,Speina, El?bieta,Winiewska‐szajewska, Maria
supporting information, (2021/06/09)
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.
BOIMPYs: Rapid Access to a Family of Red-Emissive Fluorophores and NIR Dyes
Patalag, Lukas J.,Jones, Peter G.,Werz, Daniel B.
supporting information, p. 13340 - 13344 (2016/10/30)
A fundamental, highly fluorescent, and easily accessible scaffold derived from the BODIPY core is reported. The use of benzimidazole as a bridging ligand at the meso position enables the binding of two BF2units to provide sufficient rigidity and enhanced electron-withdrawing strength. Absorption and emission events thus take place in the red (λ≈600 nm); the fluorescence quantum yields can reach unity (0.96) and show little dependence on solvent polarity. The synthetic route was shortened to two steps starting from commercially available precursors while the preparation is modular and tolerates various pyrrole and benzimidazole moieties. Fluoride replacement by propynyl groups, various halogenations, as well as Knoevenagel-type condensations were applied to extend the versatility of these new photostable fluorophores, which we termed BOIMPYs.
