ABSTRACT
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⯵M over a period of 1â¯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.
Subject(s)
Antineoplastic Agents/pharmacology , Imidazoles/pharmacology , Organophosphorus Compounds/pharmacology , Urinary Bladder Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , Imidazoles/chemical synthesis , Imidazoles/chemistry , Male , Mice , Models, Molecular , Molecular Structure , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Organophosphorus Compounds/chemical synthesis , Organophosphorus Compounds/chemistry , Structure-Activity Relationship , Urinary Bladder Neoplasms/pathologyABSTRACT
High-field 1 H NMR T2 relaxation studies were used to characterize the changes in the physical phases of water, NaCl, and dextrose solutions over a temperature range of -65 to 15 °C. The data were analyzed with the inverse Laplace transform and with a linear fit to the logarithm of the time domain signal. Two liquid phases were detected for the NaCl and dextrose solutions at lower temperatures and assigned to low and high concentrated solution domains. The high concentrated solution domain was found to be present between -30 and -5 °C in the NaCl solution and between -55 and -5 °C in the dextrose solution. Copyright © 2017 John Wiley & Sons, Ltd.
