Prykhod'ko A. The search of new protein kinase CK2 inhibitors among derivatives of 4H-4-chromenone

The synthetic small molecular inhibitors of protein kinase CK2 on the basis of 4H-4-chromenone derivatives and their complexes with protein kinase CK2. The search of new inhibitors of CK2 using methods of molecular modeling, chemical synthesis and biochemical testing. The molecular docking, biochemical testing, chemical synthesis, TLC, spectroscopy, NMR spectrometry. On the basis of molecular docking results the derivatives of 3-aryloxychromone, flavone and tetrahalogenphtalimide have been synthesized. The methods for synthesis of novel 7 (3-dialkylamino-2-hydroxypropoxy) derivatives of 3-aryloxychromone have been developed. Structure-activity relationships (SAR) of the synthesized compounds were studied. The established binding models were used for prediction of the ways for further chemical optimization with the aim to obtain more active inhibitors. As a result of this optimization 40 nanomolar CK2 inhibitors have been developed, among them six compounds demonstrated high selectivity toward CK2 and can be used in further research to study structure and cellular functions of this protein kinase. The binding models of inhibitors with protein kinase CK2 and SAR can be used for the development of novel highly potent protein kinase inhibitors. Field of application is bioorganic chemistry.