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.
European journal of medicinal chemistry. 2019 Oct 31 [Epub ahead of print]
Michael L Stromyer, Marie R Southerland, Uttam Satyal, Rahmat K Sikder, David J Weader, Jessi A Baughman, Wiley J Youngs, Philip H Abbosh
Department of Chemistry, The University of Akron, 190 East Buchtel Commons, Akron, OH, 44325, USA., Molecular Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA., Department of Chemistry, The University of Akron, 190 East Buchtel Commons, Akron, OH, 44325, USA; Molecular Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA., Department of Chemistry, The University of Akron, 190 East Buchtel Commons, Akron, OH, 44325, USA. Electronic address: ., Molecular Therapeutics Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA. Electronic address: .