Synthesis of coumarin compounds as CK2 inhibitors.

Protein kinase CK2 is ubiquitous, essential and highly pleiotropic kinase whose abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and possible implication in viral infections. CK2 is a messenger-independent protein serine/threonine kinase with more than 300 protein substrates and is implicated in many cellular functions [1, 2]. Recently some halogen-substitute 4-methylcoumarins has shown a good biological inhibitory activity. In this work is described the synthesis of new substitute coumarins and was made a preliminary structure-activity relationship through comparison with data in literature [3]. 2 goals are persecuted: verify the importance of hydroxy group in 7 position of the 3,8-dibromo-7-hydroxy-4-methylcoumarin (DBC) [3] to maintain biological activities; study how various substituent in 4-position can influence the IC50 of literature compounds. The structures of novel coumarin compounds as CK2 inhibitors are summarized in figure.