New N-heterocyclic compound derivative Schiff bases and their Ag(I) complexes: Synthesis, characterization and activities on lung cells

The widespread presence of nitrogen-containing heterocyclic rings in the structures of many bioactive compounds in nature has attracted the attention of researchers working on this field, leading them to focus on these compound groups. In the literature review, it is seen that the biological properties of nitrogen-containing heterocyclic compounds are pharmacologically applicable in many studies and the importance of developing various synthesis designs for the investigation of their biological effects is emphasized. It has been determined that pyridine, pyrazine, quinoline, quinoxaline, indole and piperazine derivative compounds, which can be given as examples of nitrogen-containing heterocyclic rings in their structures and are also found in many natural structures, have high biological activities. Therefore, derivatives containing these units are frequently preferred among target molecules for new drug designs. Schiff bases and their metal ion complexes, which have a wide range of applications, have very important places in coordination and supramolecular chemistry. Due to their unique structural properties, these types of compounds are of great importance in medicine, environmental chemistry and dye industry. Particularly, their various and effective biological activity properties make them potential bioactive agents in pharmaceutical chemistry. Click reactions that form the 1,2,3-triazole ring enable the design of low toxicity chemical and biological modifications, contributing to the formation of very important pharmacophore structures. Within the scope of this thesis study, the synthesis of potentially bioactive new-type N-heterocyclic compounds was targeted, along with the investigation of their cytotoxic activities against A549 (lung cancer) and MRC-5 (healthy lung) cells, based on the selected compound groups and the units incorporated into the structure using various synthesis methods. For this purpose, compounds containing pyridine, pyrazine, quinoline and quinoxaline units (3, 6, 9, 11 and 14) were synthesized using various reaction methods, followed by the synthesis of N-heterocyclic aldehyde derivatives (A1-A4) via click reactions. Subsequently, these compounds (A1-A4) were subjected to Schiff base condensation reactions with amine compounds, namely the indole derivative tryptamine and the piperazine derivative 1-(2-aminoethyl)piperazine, yielding new imine ligands (L1-L8). The structures of the intermediate compounds (3, 6, 9, 11 and 14) and new type N-heterocyclic compounds (A1-A4, L1-L8) were elucidated using mass spectrometry, FT-IR, 1H and 13C NMR spectra, and, for those with single crystals (A1-A4), X-ray diffraction data. Additionally, complexation reactions were performed to examine the coordination compounds formed by the new-type N-heterocyclic compounds (A1-A4, L1-L8) with Ag(I) metal ions. These complexes were characterized using mass spectrometry, FT-IR, 1H NMR, EDX, XRD and UV-Visible spectra, and their thermal stability was investigated. The cytotoxic activities of all newly synthesized N-heterocyclic compounds, whose structures were elucidated using various spectroscopic methods, were evaluated against A549 (cancer lung cell) and MRC-5 (healthy lung cell) cells using the SRB method, and their IC50 values were determined.