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 the reaction of salicylaldehyde and 3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)aniline which is the precursor of the nilotinib molecule used in the cancer treatment. It was characterizated by using spectroscopic techniques such as 1H-NMR, 13C-NMR, 19F-NMR, 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 observed that the experimental and theoretical datas were in good agreement. The ADME and toxicity properties were investigated by using online servers. According to the results, it was concluded that the MITPIM has low toxicity and high oral bioavailability. Molecular docking simulations of the MITPIM with VEGFR2 protein (PDB ID: 2XIR) were investigated. According to molecular docking studies, the binding energy of the complex formed by the MITPIM with VEGFR2 protein (PDB ID: 2XIR) was −9.34 kcal/mol and the value was close to nilotinib’s binding score which was -9.69 kcal/mol. Molecular docking and ADMEt results shown that the newly synthesized MITPIM has the potential to be drug.