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 Aβ1-42 fibrils through in-silico studies. Methods The primary phytochemicals present in date palms were subjected to molecular docking with three different conformers of Aβ1-42 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 Å2, 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.