Synthesis, spectra, crystal, DFT, molecular docking and in vitro cholinesterase inhibition evaluation on two novel symmetrical Azine Schiff bases

Abstract

The two new azine Schiff bases AZ1 and AZ2 called (1E,2E)-1,2-bis(2,4-dimethylbenzylidene) hydrazine and (1E,2E)-1,2-bis(3-methoxylbenzylidene)hydrazine, respectively were prepared through a condensation of the appropriate substituted aldehyde and the hydrazine hydrate. The two azine structures were investigated by FT-IR, NMR techniques and determined by single crystal X-ray diffraction (XRD). AZ1 and AZ2 structures crystallize in Monoclinic and Orthorhombic systems with space groups P21/c and P212121, respectively. AZ1 molecules are interconnected with hydrogen bonds CH…π and the crystal structure of AZ2 is stabilized by weak intermolecular hydrogen bonds CH…O. Theoretical calculations have been carried out at DFT/B3LYP level for the optimized geometries and TD-DFT methods. The results show an excellent agreement with the experimental data (Spectroscopic and XRD). Docking studies were performed to examine potential inhibitions of the designed azines against cholinesterases. The activities effect considering the enzymes: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are evaluated in vitro and the results show that both Azines AZ1 and AZ2 are moderate AChE inhibitors (IC50 = 23.60±0.63 µg/mL; IC50 = 28.59±0.07 µg/mL, respectively). The BChE measurements indicated an important inhibition activity of AZ1 (IC50 = 57.88±0.045 µg/mL) and no activity of AZ2.The results of these tests were in sync with the docking.