New more polar symmetrical bipyridinic compounds: new strategy for the inhibition of choline kinase α1

AIK: Research of the antitumor properties of biscationic compounds has received significant attention over the last few years. Results: A novel family of 1,1'-([2,2'-bi-pyridine]-5,5'-diylbis(methylene)) bis-substituted bromide (9a-k), containing two nitrogen atoms in the linker, considered as hypothetical hydrogen bond acceptors, were synthesized and evaluated as ChoK inhibitors and their antiproliferative activity against six cancer cell lines. Conclusion: The most promising compounds in this series are 1,1'-([ 2,2'-bi-pyridine]-5,5'-diylbis(methylene)) bis(4-(methyl-(phenyl) amino)-quinolinium bromide derivatives 9g-i (analogs to RSM932A), that significantly inhibit cancer cell growth at even submicromolar concentrations, especially against leukemia cells. Compounds 9g-i also inhibit the ChoK alpha 1 with good or moderate values, as predicted by initial docking studies. In addition, the most active compound 9h remarkably induces apoptosis in two cell lines following the mitochondrial pathway.