title: 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.
authors.affiliation: Institut für Biochemie, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Straße 2, D-48149 Münster, Germany.
authors.forename: Da
authors.initials: D
authors.lastname: Wang
authors.affiliation: Organisch Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Richter
authors.affiliation: Organisch Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rühling
authors.affiliation: Institut für Biochemie, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Straße 2, D-48149 Münster, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hüwel
authors.affiliation: Organisch Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany. Electronic address: glorius@uni-muenster.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Glorius
authors.affiliation: Institut für Biochemie, Westfälische Wilhelms-Universität Münster, Wilhelm-Klemm-Straße 2, D-48149 Münster, Germany. Electronic address: gallah@uni-muenster.de.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Galla
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D051381:Rats; D013501:Surface-Active Agents / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D013501:Surface-Active Agents
keywords: 4,5-dialkylimidazolium salt; Anti-tumor activity; Cytotoxicity