Design, synthesis and biological evaluation of new embelin derivatives as CK2 inhibitors
| Autor: | Gabriela Egly Feresin, Joachim Jose, Ángel Amesty, Pedro Martín-Acosta, Alejandro Tapia, Dagmar Aichele, Ana Estévez-Braun, Samer Haidar, Sandra Oramas-Royo |
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| Rok vydání: | 2019 |
| Předmět: |
Drug Evaluation
Preclinical 01 natural sciences Biochemistry Binding Competitive chemistry.chemical_compound Structure-Activity Relationship Adenosine Triphosphate Derivative (finance) Furan Drug Discovery Benzoquinones Humans Casein Kinase II Furans Molecular Biology IC50 Protein Kinase Inhibitors Biological evaluation 010405 organic chemistry Chemistry Organic Chemistry Combinatorial chemistry 0104 chemical sciences Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Design synthesis Docking (molecular) Drug Design Michael reaction MCF-7 Cells Knoevenagel condensation |
| Zdroj: | Bioorganic chemistry. 95 |
| ISSN: | 1090-2120 |
| Popis: | A new series of furan embelin derivatives was synthesized and characterized as ATP-competitive CK2 inhibitors. The new compounds were efficiently synthesized using a multicomponent approach from embelin (1), aldehydes and isonitriles through a Knoevenagel condensation/Michael addition/heterocyclization. Several compounds with inhibitory activities in the low micromolar or even submicromolar were identified. The most active derivative was compound 4l (2-(tert-butylamino)-3-(furan-3-yl)-5-hydroxy-6-undecylbenzofuran-4,7-dione) with an IC50 value of 0.63 μM. It turned out to be an ATP competitive CK2 inhibitor with a Ki value determined to be 0.48 μM. Docking studies allowed the identification of key ligand-CK2 interactions, which could help to further optimize this family of compounds as CK2 inhibitors. |
| Databáze: | OpenAIRE |
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