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

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 inves-tigated 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, re-spectively. AZ1 molecules are interconnected with hydrogen bonds C -H...pi and the crystal structure of AZ2 is stabilized by weak intermolecular hydrogen bonds C -H...O. Theoretical calculations have been car-ried out at DFT/B3LYP level for the optimized geometries and TD-DFT methods. The results show an excel-lent 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 consider-ing 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 mu g/mL; IC50 = 28.59 +/- 0.07 mu g/mL, respectively). The BChE measurements indicated an important inhibition activ-ity of AZ1 (IC50 = 57.88 +/- 0.045 mu g/mL) and no activity of AZ2.The results of these tests were in sync with the docking.(c) 2023 Elsevier B.V. All rights reserved.