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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry
-
Antineoplastic Agents / pharmacology*
-
Cell Line
-
Cell Proliferation / drug effects
-
Choline Kinase / antagonists & inhibitors*
-
Choline Kinase / metabolism
-
Dose-Response Relationship, Drug
-
Drug Screening Assays, Antitumor
-
Humans
-
Models, Molecular
-
Molecular Structure
-
Protein Kinase Inhibitors / chemical synthesis
-
Protein Kinase Inhibitors / chemistry
-
Protein Kinase Inhibitors / pharmacology*
-
Pyridinium Compounds / chemical synthesis
-
Pyridinium Compounds / chemistry
-
Pyridinium Compounds / pharmacology*
-
Quinolinium Compounds / chemical synthesis
-
Quinolinium Compounds / chemistry
-
Quinolinium Compounds / pharmacology*
-
Structure-Activity Relationship
Substances
-
Antineoplastic Agents
-
Protein Kinase Inhibitors
-
Pyridinium Compounds
-
Quinolinium Compounds
-
CHKA protein, human
-
Choline Kinase