2‐Aryl Imidazolium Salts as Potential Bladder Cancer Chemotherapeutic Candidates

As potential intravesical exfoliants for the treatment of bladder cancer, four new imdiazolium salts have been prepared. These compounds are modified on the nitrogen positions of the 4,5‐diphenyl‐1H‐imidazole or benzimidazole rings with naphthalen‐2‐ylmethyl groups, and the 2 positions on the azolium cations are occupied by arene rings. The 4,5‐diphenyl‐1H‐imidazole and benzimidazole precursors are produced from 1,2‐phenylenediamine and benzil respectively, and the imidazolium cations are generated from sequential alkylation of the nitrogen positions using 2‐bromomethyl naphthalene. The four imidazolium salts were screened for their chemotherapuetic activity using the NCI‐60 Human Tumour Cell Line Screen, and we observed that the cytotoxicity was more dependent on the identity of the imidazolium group (benzimidazolium versus diphenylimidazolium) rather than on the 2‐aryl position structure. We present four new naphthalene modified lipophilic imidazolium salts as potential exfoliating bladder chemotherapeutics. All exhibit tumor cell growth inhibition but show varying degrees of cytotoxicity.