Natural inhibitors of DYRK1A as drug candidates against Alzheimer Disease: QSAR, molecular docking, molecular dynamics simulation and drug evaluation assessment

Abstract Alzheimer’s disease (AD) is a dementia neurodegenerative disorder with complex mechanisms and no cure that gradually leads to loss of learning, remembering, imagining, and recalling past events. It is most commonly found in adults aged 65 and up. The research scientists are interested in producing new drugs and new drug targets that can cure or inhibit this incurable disease. The In-silico technique was used to investigate the inhibitory activities of Natural inhibitors of DYRK1A against AD. All the ligands, including the reference drug, were docked using molecular docking. The docked complex was validated experimentally with the aid of molecular dynamics simulation. Trajectory plots of compound 19 were evaluated using RMSD, RMSF, Rg, SASA, and Ligand hydrogen bonds. This stability of compound 19 was further confirmed by the RMSF, Rg, SASA, and ligand hydrogen bond. Evidently, compound 19 may have undergone alteration and formed more H-bonds with macromolecules during the 100 ns simulation than harmine (the reference drug), therefore, compound 19 has been more stable. The three ligands emerged with better docking values than the reference drug, which shows that the compounds have therapeutic ability to hinder or cure the damage caused by this disease. Also, the ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) proved that the ligands have good pharmacokinetic abilities. It is obvious from the aforementioned results that the generated model is good and are highly potent, non-toxic, and penetrate the BBB (blood-brain barrier) so as to circumvent the effect of the AD.