Anti-tumor activity and cytotoxicity in vitro of novel 4,5-dialkylimidazolium surfactants

Abstract

Natural monoalkylated imidazolium derivatives exhibit significant anti-tumor activity as well as general cytotoxicity. In the present study, we used a series of newly synthesized imidazolium derivatives bearing two alkyl chains in the backbone of the imidazolium core in 4- and 5-position and either dimethyl- or dibenzyl-substituents at 1- and 3-position. Their anti-tumor activity and cytotoxicity were determined in vitro using the lactate dehydrogenase (LDH) assay. The tumor cell line C6 from rat glioma, the non-tumor MDCK cell line (Madin–Darby canine kidney) as well as the mouse embryonic fibroblast cell line (NIH3T3) were used as cellular targets. Surface activity measurements were performed leading to the determination of their critical micelle concentration (CMC) of these new lipid analogues to evaluate the molecular mechanism of the observed cellular effects. We found that 4,5-dialkylation of the imidazole ring enhances the anti-tumor activity compared to simple 1-alkylated imidazoles. The corresponding C7 homologues are found to be the most potent compounds. Furthermore dibenzyl-substituted imidazolium surfactants exhibit higher surface activity and increased toxicity against tumor cells compared to dimethyl-substituted imidazolium surfactants. In summary the dibenzyl-derivative carrying the two C7 chains was found to exhibit a drastically increased anti-tumor activity especially compared to so far known monoalkylated species.