Determination of antioxidant capacities of newly synthesized indole derivatives and investigation of their effects on human liver cancer cells

Free radicals contain unmapped electrons moleculesin their final orbits that cause unstability in their structures. They try to get electrons from other molecules to make them stable. As a result, they cause unwanted oxidation reactions, leading to various cellular damage such as DNA damage, lipid peroxidation, protein modifications. The body's defense system against the harmful effects of free radicals is called antioxidants. Antioxidant molecules prevent the harmful effects of free radicals by attaching free radicals to themselves, transferring hydrogen to them, or repairing biomolecules damaged by free radicals. The antioxidants may be of an enzymatic structure such as glutathione-S-transferase or a non-enzymatic structure such as vitamin C. In this thesis, the antioxidant capacities of two synthesized indole derivatives, compound 1 (3-Bromo-1ethyl-2phenyl-1H-indole) and compound 2 (1-ethyl-2-phenyl-3phenylethyl-1H-indole) were determined by five different antioxidant capacities methods (DPPH, ABTS, Galvinoxyl, phosphomolybdenum and FRAP). Furthermore, Cytotoxicities of tested compounds and their effects on GST activities in HepG2 cell lines were also investigated. As a result of the study, when looking at the activity of compound 1 with 5 different antioxidant capacity determination methods, only total antioxidant activity could be determined. Compound 1 (333.3-1333.3 µM) concentrations were determined to have a potential lower than trolox (33.03-38.04 fold). It was determined that compound 2 shows antioxidant activity. It was found that when the concentration of compound 2 corresponds to trolox, where 3000 µM concentration corresponds to 47.63% RSA, it is 0.016. This shows that compound 2 had problems in terms of giving electrons. In the phosphomolybdenum method, the trolox standard was found to correspond to 1.22 times the compound 2. It was found to be close to the trolox compound value. In the FRAP method, it was calculated that compound 2 corresponds to 133.33 µM concentration and 33.83 µM trolox concentration. According to this result, it was observed that the compound 2 had antioxidant capacity, but this antioxidant capacity was low compared to the trolox standard. In the GST activity measurements, the total GST activities for control and substance treated HepG2 cells were 14.8 ± 2.4 and 0.79 ± 0.04 nmol/min/mg protein, respectively. These results showed that compound 1 treatment caused a % 94,7 reduction in GST enzyme activity. GST enzyme activities of compound 2 treatments at 25 and 50 µM concentrations were found to be 21.6 ± 2.5 and 19.3 ± 0.95 nmol/min/ mg protein, reciprocally. Compound 2 caused statistically significant induction of GST activity at 25 µM in HepG2 cell line. On the other hand, compound 2 increased GST activity at 50 µM, but this increase was not statistically significant. When the cell viability rates of the indole derivatives (compound 1 and 2) tested in this study with the cytotoxicity test, compound 1 decreased cell viability at 6.25-125 µM concentration range and the EC50 value was found to be 92 µM in the HEPG2 cell line. With this result, it has been shown that compound 1 has a highly selective cytotoxicity against the HEPG2 cell line. No statistically significant cytotoxic activity was observed at the doses of compound 2 between 6.25-250 µM.