In silico exploration of a symmetrical acridine derivative’s anti-Alzheimer activity: Synthesis, AChE/BuChE binding, and ADMET prediction.

Alzheimer’s disease (AD) figures among the most triggering neurodegenerative disorders, constituting a constant subject of interest for medicinal chemistry researchers. The treatment of such disorders remains a challenge due to the complexity of their pathogenesis. Indeed, many factors are involved in the development of AD including different enzymes such as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) which inhibition results in anti-AD activity, making the conception of novel AChE/BuChE inhibitors a possible way to manage Alzheimer’s disease. Acridine compounds constitute a known class of heterocycles with many interesting pharmacological activities, the fact that prompted us to investigate the anti-AD activity of a synthesized symmetrical acridine derivative easily synthesized from the condensation of an enaminone derivative and p-fluorobenzaldehyde under microwave irradiation. The docking study was completed using Glide software (Schrodinger suites), and both AChE (pdb: 4EY6) and BuChE (4BDS) were utilized as drug targets. The molecular docking simulation resulted in satisfying docking score values alongside numerous significant interactions indicating the high stability of the investigated compound within the active sites of studied enzymes. Additionally, ADMET prediction was carried out for the assessed acridine derivative in order to explore its drug likeness through its pharmacokinetics and toxicity profiles employing SwissADME, MolSoft, and ProTox-II online servers.