Imidazole Based Novel Schiff Base: Synthesis, Characterization, Quantum Chemical Calculations, In Silico Investigation of ADMEt Properties and Molecular Docking Simulations against VEGFR2 Protein

Abstract

The potential drug candidate novel Schiff base, 2-(((3-(4-methyl-1H-imidazol-1-yl)5-(trifluoromethyl)phenyl)imino)methyl)phenol (MITPIM) was synthesized by using salicylaldehyde and 1-[3-Amino-5-(trifluoromethyl)phenyl]-4methylimidazole, the precursor of nilotinib used in cancer treatment. It was characterized by using spectroscopic techniques such as 1H-NMR, 13C-NMR, 19FNMR, FT-IR, and UV-Vis. DFT computational technique was used for further investigation. DFT/B3LYP method and the 6-311G(d,p) basis set were used to determine optimized geometry. Then by using optimized geometry and DFT approach three-dimensional molecular electrostatic potential (MEP), vibration frequencies, NMR chemical shift values, HOMOs-LUMOs, and molecular orbital energies were calculated. It was noted that there was good agreement between the experimental and theoretical findings. The ADME and toxicity properties were investigated by using online servers. It was determined from the findings that the MITPIM had good oral bioavailability and minimal toxicity. By using 2XIR protein, the molecular docking simulations of MITPIM were also investigated. The binding energy of the MITPIM-2XIR complex was determined as −9.34 kcal/mol. It was close to nilotinib’s binding energy which was −9.69 kcal/mol. Molecular docking and ADMEt results show that the newly synthesized MITPIM has the potential to be a drug.