Biological evaluation of 4,5,7-trisubstituted Indeno[1,2-<em>b</em>]indoles reveals a potent inhibitor of protein kinase CK2 in tumor cells with diverse anti-cancer effects and preferential cytoplasmic localization

• DOI: 10.3390/ecmc2021-11450
• Publication Date: 2021-12-16T07:56:07Z
• Authors: Ehab El-Awaad; Robin Birus; Laurens Ballentin; Faten Alchab; Dagmar Aichele; Laurent Ettouati; Claudia Götz; Marc Le Borgne; Joachim Jose
• Keywords: IC50; Intracellular pH

The highly pleiotropic and constitutively active serine/threonine protein kinase CK2 is considered a key target in cancer. indeno[1,2-b]indole scaffold was previously shown to provide derivatives exhibiting strong inhibition satisfactory drug-like characteristics. In this work, we evaluated one 4,5,7-trisubstituted derivative for its intracellular of activity the accompanying effects on proliferation, migration apoptosis cancer cells. compound 5-isopropyl-4-methoxy-7-methyl-5,6,7,8-tetrahydro-indeno[1,2-b]indole-9,10-dione (5a-2) strongly inhibited vitro with IC50 value 25 nM cultured A431, A549 LNCaP cell lines (> 75% at 20 µM). by 5a-2 comparable that induced reference inhibitor CX-4945, though latter exhibited > 6-fold higher inhibitory potency toward (IC50 = 3.7 nM). A possible explanation discrepancy significantly concentrations compared CX‑4945 following their cellular uptake. Compared similar anti-proliferative, weaker pro-apoptotic but stronger anti-migratory These variations can be partly attributed observed differences subcellular localization both compounds whereby 71% uptaken molecules were found cytoplasm while 49% CX-4945 detectable nuclear fraction. Our study emphasizes potential as an interesting framework developing potent inhibitors highlights significance distribution dictating preferential inhibitors.