Anti-aggregation potential of polyphenols from Ajwa date palm (Phoenix dactylifera): An in-silico analysis

Background: Amyloid β (Aβ) fibril agglomeration is crucial in Alzheimer's disease (AD) etiology, leading to significant harm to the central nervous system. Polyphenols have been investigated for their capacity to hinder Aβ agglomeration. Objective: This investigation aimed to assess the potential of Ajwa date palm (Phoenix dactylifera)-based bioactives in binding and disrupting resilient Aβ_1-42 fibrils through in-silico studies. Methods: The primary phytochemicals present in date palms were subjected to molecular docking with three different conformers of Aβ_1-42 and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis. The stability of the system was assessed through molecular dynamics (MD) simulation. Results: It was noted that Diosmetin, Rutin, and Genistein effectively bind with 2BEG, 2MXU, and 2NAO fibrils, respectively, with docking energies ranging from −7.2 to −8.2 kcal/mol. Diosmetin, Rutin, and Genistein show notable pharmacokinetic variability, with LogP values from −1.69–2.58, with 1–6 rotatable bonds, and total polar surface areas (TPSA) between 112.52 and 240.90 Ų, characteristics important for drug candidacy evaluation. Their ADMET properties include solubility values of −3.238 to −3.595 mol/L, intestinal absorption of 23.4–93.4%, and VDss ranging from 0.094 to 1.663 L/kg. The ensuing MS simulations spanning 100 ns, illuminated the establishment of a robust peptide-chemical complex. Hydrophobic interactions, ionic and hydrogen bonds play a critical role in the ligand binding with their respective targets. Conclusions: These findings underscore the potential of these botanicals as leads for developing potent Aβ agglomeration inhibitors. However, before introducing into clinical settings, these findings need to be validated further.