Potential Anticancer Activity and Toxicity of Novel Triazole Compounds Containing 5-Fluorouracil Sugar Derivative
Project no. 23138 · Status: Kapanmış · 2021
Summary
<p>Cancer has become a very common disease with a high lethality the whole world also in our land. Drugs used in cancer treatments aim to destroy rapidly growing cancer cells without harming healthy cells. Thanks to developing science and technology are looking for new drug alternatives that have less side effects and higher success rates in tumor cells. 5-Fluorouracil (5-FU) which is one of the first-line drugs used in general treatment of especially solid tumors such as, head, stomach, pancreas, breast and neck. Considering the effective bioactivities and ease of use of triazole compounds and the limitations and difficulties in the use of 5-FU, it is expected that the newly formed triazole compounds containing 5-FU sugar derivatives will show the desired properties against cancer. The aim of the thesis is to investigate the cytotoxic, genotoxic, apoptotic and anti-angiogenic properties of newly synthesized triazole compounds containing 5-FU and to evaluate these compounds in terms of toxicity and biological effect. Within the scope of these study in new triazole compounds containing 5- FU, MTT test to determine the in vitro cytotoxic effect, Flow Cytometry analyzes to determine apoptosis, AMES test to determine genotoxic potential and HETCAM test to observe angiogenic/antiangiogenic effects were performed. It was revealed that the compounds whose IC50 values were calculated after the MTT test had a lower cytotoxic effect than the positive control. The 1xIC50 and 2xIC50 values of the compounds were calculated with the values obtained in consequence of tests and the apoptotic activity was examined and apoptosis as well as predominantly necrosis were detected in the results. Conclusion of the AMES test, no genotoxic effect was observed in the compounds even at the maximum concentration of 5000 µg/mL effects were determined. It was determined that the compounds showed anti-angiogenic effects in all concentration (4-2-1-0.5-0.25 µg/mL) assays with the HET-CAM test. As a result, it has become found by in vitro assays which substances are less toxic and at the same time more effective. More precise results should be supported by in vivo assays.</p>