Synthesis and antitumor activity of steroid-based imidazolium salts

A total of thirty-six novel diosgenin-, cholesterol-, and dehydroepiandrosterone-imidazolium salt derivatives were synthesized and their cytotoxic activities were evaluated <i>in vitro</i> against a panel of human tumor cell lines. The SAR results indicated that the presence of a substituted 5,6-dimethylbenzimidazole ring and the substitution at the imidazolyl-3-position with a 1-naphthylmethyl or 4-methylbenzyl group could be critical for enhancing cytotoxic activity. Dehydroepiandrosterone-imidazolium salt 12f was found to be the most potent compound with IC₅₀ values of 1.07-2.10 μM against MDA-MB-231, HepG2 and 22RV1 human tumor cell lines. Furthermore, cell cycle and apoptosis experiments of compound 12f were carried out and the results showed that 12f could induce G0/G1 cell cycle arrest and apoptosis in HepG2-116 cells.