Assessment of the Interaction of Acetylcholinesterase Binding with Bioactive Compounds from Coffee and Coffee Fractions Digested in the Gastrointestinal Tract.

The aim of the study was to evaluate the degree of acetylcholinesterase (AChE) inhibition by green and light- and dark-roasted coffee extracts and their fractions after digestion in a simulated gastrointestinal tract. The analysis was carried out using isothermal titration calorimetry, molecular docking, and dynamics simulations. The results showed that 3--caffeoylquinic acid binds strongly to AChE through hydrogen interactions with the amino acids ARG289A, HIS440A, and PHE288A and hydrophobic interactions with TYR121A in the active site of the enzyme. The Robusta green coffee extract (Δ = -35.87 kJ/mol) and dichlorogenic acid fraction (Δ = -19-29 kJ/mol) showed the highest affinity. Dichlorogenic acids (3,4--dicaffeoylquinic acid, 4,5--dicaffeoylquinic acid, and 3,4--dicaffeoylquinic acid) have high affinity for AChE as single compounds (Δ(ITC) = -48.99-55.36 kJ/mol, Δ(LF/AD) = -43.38-45.38 kJ/mol). The concentration necessary to reduce AChE activity by 50% amounted to 0.22 μmol/μmol chlorogenic acids to the enzyme.