Synthesis, characterization, and in vitro SAR evaluation of N,N′-bis(arylmethyl)-C2-alkyl substituted imidazolium salts

• Published in: Bioorganic & medicinal chemistry letters 2017-01, Vol.27 (2), p.196-202
• Main Authors: DeBord, Michael A., Wagers, Patrick O., Crabtree, Steven R., Tessier, Claire A., Panzner, Matthew J., Youngs, Wiley J.
• Format: Article
• Language: English
• Subjects: Anti-cancer; Anti-tumor; Imidazolium salt; Naphthalene; Non-small cell lung cancer; Quinoline
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2016.11.075

[Display omitted] 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.