Synthesis, characterization, and biological activity of a triphenylphosphonium-containing imidazolium salt against select bladder cancer cell lines.

Imidazolium salts have shown great promise as anticancer materials. A new imidazolium salt (TPP1), with a triphenylphosphonium substituent, has been synthesized and evaluated for in vitro and in vivo cytotoxicity against bladder cancer. TPP1 was determined to have a GI50 ranging from 200 to 250 μM over a period of 1 h and the ability to effectively inhibit bladder cancer. TPP1 induces apoptosis, and it appears to act as a direct mitochondrial toxin. TPP1 was applied intravesically to a bladder cancer mouse model based on the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Cancer selectivity of TPP1 was demonstrated, as BBN-induced tumors exhibited apoptosis but normal adjacent urothelium did not. These results suggest that TPP1 may be a promising intravesical agent for the treatment of bladder cancer.