Determination of anticancer activities of some synthetic compounds

Nowadays, it is known that therapeutic activity of drugs of the anthraquinone group which are widely used in various cancer types could increase by adding different side substitute to them and these new synthesized anthraquinone derivatives could prevent development of resistance in cancer cells. Therefore, a wide range of anthraquinone derivatives are synthesized and their apoptotic effect mechanisms are studied in details. In this thesis, cytotoxic and apoptotic effects of newly synthesized anthraquinone eight derivatives on HeLa cell line were investigated. IC50 values of derivatives were investigated by 3-(4,5-dimetiltiazol-2yl)-2,5 difenil tetrazolium bromid (MTT) method. After 24 hour, Ant 3 (IC50; 10 ?M), Ant 4 (IC50; 8 ?M) and Ant 6 (IC50; 8 ?M) were detected that the most effective derivatives compared to others. In line with these results, the effects on HeLa cell apoptosis of IC50 values and lower doses of these derivatives were investigated in details. Early apoptotic cell ratio, which was measured by Annexin V-FITC method, increased to % 12.9 after incubation time for 6 hour of Ant 6. This ratio was detected as % 2.0 for 2.6 ?M mitoxantrone. According to this, Ant 6 induced early apoptosis of cells effectively relatively mitoxantrone and the other derivatives. At the same time, apoptotic index based on DNA fragments in cells which were incubated with Ant 6 (3 ?M) in 24 hour was indicated as % 54. As for results of caspase-3 activation, caspase-3 level increased to % 18 after incubation of Ant 3 for 12 hour. As a result, each of three derivatives induced apoptosis of HeLa cells more effectively than mitoxantrone at lower doses after short incubation time. These anthraquinone derivatives, which have chemotherapeutic potential, will be useful for cancer treatment after in vivo studies.