Anti-tumor activity of lipophilic imidazolium salts on select NSCLC cell lines

Abstract

The anti-tumor activity of imidazolium salts is highly dependent upon the substituents on the nitrogen atoms of the imidazolium cation. We have synthesized and characterized a series of naphthalene-substituted imidazolium salts and tested them against a variety of non-smallcell lung cancer cell lines. Several of these complexes displayed anticancer activity comparable to cisplatin. These compounds induced apoptosis in the NCI-H460 cell line as determined by Annexin V staining, caspase-3, and PARP cleavage. These results strongly suggest that this class of compounds can serve as potent chemotherapeutic agents.

Synthesis, anti-proliferative activity, SAR study, and preliminary in vivo toxicity study of substituted N,N′-bis(arylmethyl)benzimidazolium salts against a panel of non-small cell lung cancer cell lines

“…A distinctive resonance for the C 5 (C 6 ) substituted benzimidazolium salts ( 2–8 ) was the C 2 proton, which was observed within the range of 9.84–10.30 ppm and was consistent with the C 2 proton of 1 (10.14 ppm). [5] In the 1 H NMR spectra of 2–8 , appearance of singlet resonances in the range of 5.50–6.09 ppm corresponded to the methylene linker between the naphthalene groups and the nitrogen atoms of the benzimidazole ring. Furthermore, the 1 H NMR spectra of 2 and 3 showed singlet resonances at 3.83 ppm and 3.86 ppm, which corresponded to the methyl carbon in the ether and ester substituents at the C 5 position.…”

“…In the 1 H NMR spectra of 24 – 25 , the appearance of a singlet resonance observed in the range of 6.19–6.21 ppm, corresponding to the methylene linker between the quinoline groups and nitrogen atom of the benzimidazolium cation, is consistent with related compounds. [5] The methyl resonances of 24 and 25 were observed at 3.12 ppm and 2.32 ppm, by 1 H NMR spectroscopy and were indicative of the methyl alkyl substituents at the C 2 and C 5 (C 6 ) positions, respectively. Compound 24 , was characterized by single-crystal X-ray crystallography (Figure 12).…”

“…[5] However, 1 was limited by poor aqueous solubility, and therefore does not have the potential to be systemically administered. Compounds 2–25 and 28–31 were synthesized to establish a SAR and discover benzimidazolium salts with the potential to be used clinically.…”

“…[5,6] The highly lipophilic N,N ′-bis(naphthylmethyl)imidazolium salt 1 exhibited high anti-proliferative activity against several NSCLC cell lines (Figure 2). It was shown that the in vitro anti-tumor activity of 1 was strongly correlated to the two naphthylmethyl substituents at the N 1 and N 3 positions of the imidazole ring.…”

Imidazolium Salts as Small-Molecule Urinary Bladder Exfoliants in a Murine Model

“…Compounds 1 and 2 were synthesized according to a published procedure (32). To synthesize the remaining compounds, the imidazole derivatives were alkylated in two steps (Fig.…”