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.

Automated summary

Two new azine Schiff bases, AZ1 and AZ2, were prepared through a condensation reaction between appropriate substituted aldehydes and hydrazine hydrate. The structures of AZ1 and AZ2 were determined by FT-IR, NMR, and single crystal X-ray diffraction. The theoretical calculations and docking studies showed agreement with the experimental data. In vitro evaluations indicated that both AZ1 and AZ2 exhibited moderate inhibition activity against acetylcholinesterase, while only AZ1 exhibited inhibition activity against butyrylcholinesterase.