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 IC₅₀ values 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.

Keywords: Anti-cancer; Anti-tumor; Imidazolium salt; Naphthalene; Non-small cell lung cancer; Quinoline.