Abstract
Aim: 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′-bipyridine]-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′-bipyridine]-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 ChoKα1 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.
Financial & competing interests disclosure
We thank the Fondazione Cariparo by the ‘Progetto Ricerca Pediatrica’. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. The authors gratefully acknowledge the ‘Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía’ (Excellence Research Project: P07-CTS-03210) and the ‘Ministerio de Ciencia e Innovación’ (SAF2009–11955) for the financial support, the award of grants from ‘Ministerio de Educación’ to P Ríos-Marco is gratefully acknowledged, and the ‘Centro de Servicios de Informática of the University of Granada (Spain) for the use of their computers and scientific software. G Viola, E Mariotto and G Basso. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.