Abstract
Aim: Choline kinase α inhibitors represent one of the newest classes of cytotoxic drugs for cancer treatment, since aberrant choline metabolism is a characteristic shared by many human cancers. Results: Here, we present a new class of asymmetrical pyridinium/quinolinium derivatives developed and designed based on drug optimization. Conclusion: Among all compounds described here, compound 8, bearing a 7-chloro-4N-methyl-p-chloroaniline quinolinium moiety, exhibited the greatest inhibitory activity at the enzyme (IC50 = 0.29 μM) and antiproliferative activity in cellular assays (GI50 = 0.29–0.92 μM). Specifically, compound 8 strongly induces a cell-cycle arrest in G1 phase, but it does not significantly induce apoptosis while causing senescence in the MDA-MB-231 cell line.
Plain Language Summary
Graphical abstracts
Financial & competing interests disclosure
The authors thank to University of Granada, Cei-Biotic Projects CEI2013-MP-1 from University of Granada for the financial support. 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.