Synthesis, characterization, theoretical calculations of new schiff bases, investigation of their antimicrobial activities in vitro and in silico

In this thesis, two new Schiff bases (DBT and DBN) were synthesized by separate condensation reactions of 4-dimethylamino benzaldehyde with 3,4-diaminotoluene and 1,8-diaminonaphthalene. The structures of the synthesized molecules were elucidated by 1H- and 13C-NMR, mass, FT-IR and UV-vis spectroscopy. Optimized geometries, molecular electrostatic potential (MEP) diagrams and frontier molecular orbitals (HOMO/LUMO) of the molecules were calculated using density functional theory (DFT), B3LYP method and 6-311G(d,p) basis set. 1H- and 13C-NMR, FT-IR and UV-vis spectral data of DBT and DBN molecules were also calculated at the same level and it was determined that the theoretical data obtained were compatible with the experimental ones. Potential energy surface (PES) calculations of the molecules were also carried out within the framework of the selected dihedral angles, and the most stable and unstable conformations were obtained. In addition, the intramolecular non-covalent interactions (NCI) of the synthesized compounds were examined and the results were visualized with a reduced density gradient (RDG) scatter plot. The ADMET parameters of the new synthesized Schiff bases were examined in silico and some druglikeness, physicochemical, lipophilicity and pharmacokinetic parameters of these molecules were determined. The potential antimicrobial activities of DBT and DBN compounds were primarily studied by the molecular docking method. Lipoteichoic acid synthase and β-ketoacyl-ACP synthase III proteins were used in molecular docking studies and it was determined that the best binding occurred between lipoteichoic acid synthase and DBT with a binding energy of -9.2 kcal/mol. As a result of molecular docking studies, molecular dynamics simulation studies of the ligand-protein complex with the best binding energy were also carried out for 100 ns and it was concluded that the complex maintained its stability under physiological conditions. In vitro antimicrobial studies of both molecules were also carried out, and results consistent with in silico studies were achieved.