New benzimidazole derivatives containing hydrazone group as anticancer agents: Inhibition of carbonic anhydrase IX and molecular docking studies

In this study, we propose identifying potential novel compounds targeting carbonic anhydrase (CA) IX and anticancer activity. To study the impact of these synthesized compounds on CA IX and anticancer activity, we have developed and synthesized novel benzimidazole-hydrazone derivatives (3a-3j). The target compounds' H-1 NMR (nuclear magnetic resonance), C-13 NMR, and high resolution mass spectrometry spectra were used to confirm their chemical structures. L929 (healthy mouse fibroblast cell line) used as control healthy cell line and MCF-7 (breast cancer), C6 (rat glioblastoma), HT-29 (colon cancer), cells were used in cell culture studies. As a result of cell culture studies, it was determined that the newly synthesized compounds 3d and 3j had cytotoxic effects on colon cancer. Again, it was determined that the compound 3d had a more toxic effect than cisplatin on both breast cancer and glioma cells. According to the CA IX activity results, compounds 3d and 3j were found to have the highest activity. Compounds 3d and 3j are essential for having anti-cancer properties and inhibiting the carbonic anhydrase IX enzyme. Molecular docking of these compounds was carried out in the active site of CA IX. Flow cytometry and immunofluorescence microscope analyses also confirmed that these compounds had cytotoxic effects on cancer cells.