Evaluation of the Alkaloids as Inhibitors of Human Acetylcholinesterase by Molecular Docking and ADME Prediction.

Background/aim: Alzheimer's disease is a complex, incurable to date, multifactorial disease, which suggests the need for continued development of pharmacotherapy.

Materials and methods: A comprehensive literature search was conducted to identify known ligands with anticholinesterase activity, resulting in the discovery of over 100 alkaloids that are also available in the PubChem database. Subsequently, the ligands underwent molecular docking to evaluate their affinity for the target enzyme. The ligands with the greatest affinity were selected for ligand-based virtual screening.

Results: Three potential compounds were identified for further investigation: ZINC000055042508, ZINC000096316348, and ZINC000067 446933. Computational models of absorption, distribution, metabolism, and excretion (ADME) properties prediction using SwissADME suggested that ZINC000055042508 and ZINC000067446933 can permeate the blood-brain barrier and exhibit non-substrate behavior with respect to P-glycoprotein. In contrast, the ProTox-III prediction indicated the potential for all three compounds to penetrate the blood-brain barrier.

Conclusion: These alkaloid derivatives warrant further investigation as potential acetylcholinesterase inhibitors for the treatment of Alzheimer's disease.