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.
DeBord, M. A., Wagers, P. O., Crabtree, S. R., Tessier, C. A., Panzner, M. J., & Youngs, W. J. (2017). Synthesis, characterization, and in vitro SAR evaluation of N,N′-bis(arylmethyl)-C2-alkyl substituted imidazolium salts. Bioorganic and Medicinal Chemistry Letters, 27(2), 196–202. https://doi.org/10.1016/j.bmcl.2016.11.075