Phytochemical constituents analysis in for Alzheimer's disease: molecular docking and in-silico toxicity approach.

Alzheimer's disease (AD) is a common brain disease associated with cognitive impairment and dementia. donepezil, an acetylcholinesterase (AChE) inhibitor drug as a commercial AD drug represents a non-cost-effective treatment with the toxic effects reported. As the prevalence of AD increases, the development of effective therapeutic treatments is urgently required. Laminaria digitata is a brown seaweed claimed to be able to prevent and treat neurodegenerative diseases. Therefore, this study measured and compared the binding affinity and toxicity of seven common phytoconstituents in against acetylcholinesterase (AChE) with those of donepezil using a molecular docking approach. The binding free energy values of donepezil, dieckol, eckol, fucodiphlorethol G, 7-Phloroecol, laminaran, alginic acid, and fucoidan with acetylcholinesterase (AChE) were -12.3, -13.5, -10.5, -8,7, -9.7, -8.0, -10.3, and -7.4 kcal/mol. All ligands constantly interacted with the AChE amino acid residues, namely Tyr124. Dieckol, with the strongest and most stable interaction, is classified as class IV toxicity, with an LD50 value of 866 mg/kg. It has aryl hydrocarbon receptor (AhR) and mitochondrial membrane potential (MMP) toxicity at certain doses. Theoretically, based on Lipinski's rule, dieckol is likely to have poor absorption and permeation properties; therefore, several considerations during the drug discovery process are needed.