title: Synthesis, characterization, and in vitro SAR evaluation of N,N'-bis(arylmethyl)-C2-alkyl substituted imidazolium salts.
abstract: A series of C2-alkyl substituted N,N'-bis(arylmethyl)imidazolium salts were synthesized, characterized, and tested for their in vitro anti-cancer activity against multiple non-small cell lung cancer cell lines by our group and the National Cancer Institute's-60 human tumor cell line screen to establish a structure-activity relationship. Compounds are related to previously published N,N'-bis(arylmethyl)imidazolium salts but utilize the historical quinoline motif and anion effects to increase the aqueous solubility. Multiple derivatives displayed high anti-cancer activity with IC50values in the nanomolar to low micromolar range against a panel of non-small cell lung cancer cell lines. Several of these derivatives have high aqueous solubilities with potent anti-proliferative properties and are ideal candidates for future in vivo xenograft studies and have high potential to progress into clinic use.
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: DeBord
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, United States.
authors.forename: Patrick O
authors.initials: PO
authors.lastname: Wagers
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, United States.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Crabtree
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, United States.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Tessier
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, United States. Electronic address: mjp9@uakron.edu.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Panzner
authors.affiliation: Department of Chemistry, University of Akron, Akron, OH 44325, United States. Electronic address: youngs@uakron.edu.
authors.forename: Wiley J
authors.initials: WJ
authors.lastname: Youngs
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles
keywords: Anti-cancer; Anti-tumor; Imidazolium salt; Naphthalene; Non-small cell lung cancer; Quinoline