Association mechanism of four acetylcholinesterase inhibitors (AChEIs) with human serum albumin: a biochromatographic approach.
In this work, the interaction of a series of acetylcholinesterase inhibitors (AChEIs; donepezil, galanthamine, huperzine and neostigmine) with human serum albumin (HSA) immobilized on porous silica particles was studied using a biochromatographic approach. For all the tested AChEI molecules, linear retention plots were observed at all temperatures. An analysis of the thermodynamics (i.e. enthalpy (DeltaH degrees ), entropy ((S degrees *)) of the interaction of the AChEI molecules with the immobilized human serum albumin was also carried out. The (H degrees and (S degrees * values for donepezil, galanthamine and neostigmine, were negative due to van der Waals interactions and hydrogen bonding which govern this association with albumin. Whereas the positive values of (H degrees and (S degrees * of huperzine binding on HSA indicated a predominance of hydrophobic interactions. The association of AChEIs with HSA was increased linearly with pH. A comparative thermodynamic study with benzodiazepine molecules was also done to determine the potential binding site of these drugs on HSA.
Ibrahim
Firas
F
Equipe des Sciences Séparatives et Biopharmaceutiques (2SB/EA-3924), Laboratoire de Chimie Analytique, Faculté de Médecine Pharmacie, Université de Franche-Comté, Place Saint Jacques, 25030 Besançon Cedex, France.
André
Claire
C
Thomassin
Mireille
M
Guillaume
Yves-Claude
YC
D001665:Binding Sites; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004800:Enzymes, Immobilized / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D002800:Cholinesterase Inhibitors; D004800:Enzymes, Immobilized; D012709:Serum Albumin; D014867:Water