Indeno[1,2-b]indole inhibitors of human protein kinase CK2 and their impact on different tumor cell lines. 2nd Electronic Conference on Medicinal Chemistry, 1.-30.11.2016

Aichele D, Le Borgne M, Jose J

Abstract

Increased protein kinase CK2 activity is involved in many human diseasessuch as cancer (1). In consequence CK2 is an emerging major target for drugdesign. Several indeno[1,2-b]indole-9,10-dione derivatives containing N5-isopropylsubstitutions on the C-Ring were synthesized and have been reported as potentATP-competitive CK2 inhibitors (2,3).Here we report on the evaluation of these inhibitors, containing differentsubstituents 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 lineA431. The most potent CK2 inhibitor contains an O-prenyl residue R1 and exhibitsan IC50 value of 0,025 μM. Treatment of MCF-7 cells with 20 μM of that compoundfor 24 h results in a reduction of the total cell number by 90%. Most of theremaining cells exhibited apoptotic morphology and showed nearly noneproliferating activity. In contrast treatment of A431 cells and A427 cells caused onlya moderate decrease of cell proliferation by 30% for all tested compounds.This study shows that potent CK2 inhibitors as tested can exhibit distinct effects ondifferent tumor cell lines. Compound containing an O-prenyl residue R1 appears tobe an antiproliferating agent with high activity toward MCF7 cells.