Indeno[1,2-b]indol Inhibitors of Human Protein Kinase CK2 and Their Impact on Different Tumor Cell Lines

Increased protein kinase CK2 activity is involved in many human diseases such as cancer (1). In consequence CK2 is an emerging major target for drug design. Several indeno[1,2-b]indole-9,10-dione derivatives containing N⁵-isopropyl substitutions on the C-Ring were synthesized and have been reported as potent ATP-competitive CK2 inhibitors (2,3).

Here we report on the evaluation of these inhibitors, containing different substituents in the A- and D-rings, for their effects on various tumor cell lines: breast cancer cells MCF-7, lung carcinoma cells A427 and epidermal cancer cell line A431.

The most potent CK2 inhibitor contains an O-prenyl residue R₁ and exhibits an IC₅₀ value of 0,025 µM. Treatment of MCF-7 cells with 20 µM of that compound for 24 h results in a reduction of the total cell number by 90%. Most of the remaining cells exhibited apoptotic morphology and showed nearly none proliferating activity. In contrast treatment of A431 cells and A427 cells caused only a moderate decrease of cell proliferation by 30% for all tested compounds.

This study shows that potent CK2 inhibitors as tested can exhibit distinct effects on different tumor cell lines. Compound containing an O-prenyl residue R₁ appears to be an antiproliferating agent with high activity toward MCF7 cells.

 References

1. Guisiano, S. et al: Eur. J. Cancer 2011, 47, 792-801
2. Alchab, F. et al : Pharmaceuticals 2015, 8, 279-302
3. Gozzi, et al: J. Med. Chem 2015, 58, 265-277