Synthesis of new hydrazone derivatives with anti-cancer effect, evaluation of their biological activities and structure-actity relationships

Cancer is one of the leading causes of death worldwide. Stomach cancer accounts for 5.6% of all cancers. H. Pylori is the most important pathogen that causes stomach cancer. Urease is known as an important enzyme for the nitrogen cycle and is very important for microbial protein synthesis and growth of microorganisms. In particular, it enables H. pylori to overcome the acidic pH and colonize bacteria in the mucus layer of the stomach environment. In this thesis study, 10 new hydrazone derivatives (3a-3j) were synthesized and their chemical structures were elucidated using NMR spectroscopy. Then, the anticancer effects of the synthesized compounds were evaluated using two different gastric cancer cells (SNU1 and AGS). The antibacterial effects of the compounds against H. pylori were examined and their inhibition potential against the urease enzyme was evaluated. When the anticancer activity results were examined, especially compound 3c was more effective against both cancer cells (IC50= 54.10±1.72 and 44.51±1.80 µM) than the reference drug cisplatin (IC50= 84.80±3.31 91.85± 2.24 µM) was found to be more effective. According to the antibacterial activity results, compound 3c was found to be the most effective compound against H. pylori among the compounds, with a MIC value of 4 µg/mL and an MBK value of 8 µg/mL. The inhibition potentials of the compounds against the urease enzyme were compared with thiourea. In particular, compounds 3b, 3c, 3f, and 3j were found to be more effective than thiourea as a positive control against urease. Molecular docking study was carried out to analyze the interaction between the active site of the enzyme (urease) and compound 3c.