Synthesis and biological determination of a new anthracen-9,10-dione derivative as a human CK2 inhibitor.

Haidar S, Meyers A, Bollacke A, J

Abstract

Casein kinase 2 (CK2) is ubiquitous kinase protein emerging as a target for several human diseases including cancer. Several active CK2 inhibitors have been developed in the last few years; most of them have ATP-competitive type of inhibition, and only one inhibitor is in clinical trial as anticancer drug. Here we report on the synthesis of two derivatives of 2,6-diaryl-anthracene-9,10-dione, one of them, 2,6-di(furan-3-yl)anthracene-9,10-dione compound 3, turned out to be active towards CK2, and ATP competitive with an IC50 value of 2.35 μM and a Ki value of 1.26 μM. Molecular modeling studies indicated that unlike emodin, compound 3 was not able to perform a hydrogen bond with Lys68, although the compound fits well in the active site of human CK2α, which explains the difference in the measured affinity between those two compounds.