Study of cytotoxicity of potential antituberculotics using selected methods on liver and kidney cell line

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Mgr. Simona Katrnošková Supervisor: PharmDr. Jana Ramos Mandíková, Ph.D. Title of Thesis: Study of cytotoxicity of potential antituberculotics using selected methods on liver and kidney cell line During pharmacologic therapy, tissues of liver and kidney are frequently exposed to high doses of xenobiotics. Via in vitro assays during preclinical testing, we are able to predict potential toxicity which helps to prevent the possible serious adverse drug reactions in clinical practice. The aim of this rigorous thesis was to state the cytotoxic profile of 4 potential antituberculotic drug candidates using appropriate cell models and in vitro assays. Another aim was to compare the cytotoxic effect of the tested compounds among themselves and to 4-aminosalicylic acid (PAS) which antituberculotic activity is known for many years. The tested substances were 3 salicylanilide diethyl phosphate-based derivatives and 4-(trifluormethyl)benzoic acid. For the cytotoxic potential assessment, we used the parameter half maximal inhibitory concentration IC50. We have used methods determining the cell metabolic activity, aminopeptidase activity, lactate dehydrogenase leakage and activity of 3/7 caspases in this..