Synthesis and biological evaluation of anthracene-9,10 dione derivatives as CK2 inhibitors

Human protein kinase CK2 is an important target for the development of anticancer drugs. Many inhibitors were developed in the last few decades, among them emodin, a natural inhibitor with anthracene-9,10-dione backbone. In this work the inhibitory activity of another natural compound endocrocin having similar chemical structure to emodin was evaluated and turned out to be a moderate inhibitor with IC50 value of 6 & mu;M. Additionally, a series of anthracene-9,10-dione derivatives was synthesized and their inhibitory activity toward the target enzyme was evaluated and compared to the activity of emodin. Only one compound namely 1-amino-6methylanthracene-9,10-dione (4i) resulted be a potent inhibitor with an IC50 value of 1.45 & mu;M. The rest of derivatives showed moderate or no inhibitory activities when were tested at 10 & mu;M concentration. Additionally, the effect of emodin, endocrocin and compound 4i was evaluated on breast cancer cells (MCF7). Using IncuCyte TM life cell monitoring, cell growth of MCF7 cells was blocked almost completely after addition of 30 & mu;M of emodin, whereas endocrocin was able to reduce cell growth by around 45%. Endocrocin with a concentration of 30 & mu;M was able to reduce the viability of MCF7 cells to around 70% after 48 h of incubation. While only 20% of MCF7 cells were still able to synthesize DNA upon incubation with 100 & mu;M endocrocin for 24 h. On the other hand, compound 4i showed weak effect on MCF7 cell line.

Automated summary

In this study, the inhibitory activity of endocrocin and its derivatives on human protein kinase CK2 was evaluated. Endocrocin was found to be a moderate inhibitor, while only one derivative showed strong inhibitory activity. Furthermore, the effects of emodin, endocrocin, and compound 4i on breast cancer cells (MCF7) were investigated.