A single-molecule with multiple investigations: Synthesis, characterization, computational methods, inhibitory...

This study reports a newly synthesized crystalline molecule with azomethine structure, (E)-1-(5-nitro-2-(piperidin-1-yl)phenyl)-N-(p-tolyl)methanimine, and its structural, spectral, topological, and electronic properties calculated by combined experimental and computational techniques. The study also presents the computational approaches to drug-like nature of the molecule. The main objective of this study is to determine the drug-like properties of the title compound and to demonstrate its acetylcholinesterase inhibitory activity for the cholinergic hypothesis of Alzheimer's disease. In this work, we synthesized the title molecule by the condensation reaction between an aromatic amine and an aldehyde and verified its molecular structure by spectroscopic techniques (X-ray, FTIR, and UV-Vis). The computational results of the title compound (MEP, FTIR, UV-Vis, FMOs, Mulliken charges, HOMO-LUMO analysis, structure optimization) were obtained at the DFT/B3LYP level using the Gaussian package program. In silico biological studies such as target identification, ADMET prediction, BBB permeation, gastrointestinal absorption, and molecular docking studies were performed using web tools or software: BindingDB, SwissTargetPrediction, admetSAR, ADMETlab, SwissADME, ProTox- II, BOILED -Egg method, and AutoDock. The ADME profile of the title compound is at the desired level and within the range of applicability. The compound was evaluated as mutagenic and carcinogenic in toxicity analyzes. The title compound can pass the BBB and be absorbed by the human gastrointestinal tract. The calculated docking score of the title compound is not better than the AChE inhibitors known as galantamine and donepezil (positive control group). The binding energies of the complexes, title compound-AChE, donepezil-AChE, and galantamine-AChE, were calculated to be -7.80, -10.41, and -8.16 kcal/mol, respectively.