Synthesis, characterization, in vitro SAR study, and preliminary in vivo toxicity evaluation of naphthylmethyl substituted bis-imidazolium salts.

A series of novel bis-imidazolium salts was synthesized, characterized, and evaluated in vitro against a panel of non-small cell lung cancer (NSCLC) cells. Two imidazolium cores were connected with alkyl chains of varying lengths to develop a structure activity relationship (SAR). Increasing the length of the connecting alkyl chain was shown to correlate to an increase in the anti-proliferative activity. The National Cancer Institute's NCI-60 human tumor cell line screen confirmed this trend. The compound containing a decyl linker chain, 10, was chosen for further in vivo toxicity studies with C578BL/6 mice. The compound was well tolerated by the mice and all of the animals survived and gained weight over the course of the study.

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

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.