Association mechanism of four acetylcholinesterase inhibitors (AChEIs) with human serum albumin: A biochromatographic approach

作者：Ibrahim Firas; Andre Claire; Thomassin Mireille; Guillaume Yves Claude^*

来源：Journal of Pharmaceutical and Biomedical Analysis, 2008, 48(5): 1345-1350.

DOI：10.1016/j.jpba.2008.09.029

• Albumin
• Acetylcholinesterase inhibitors
• Association
• Thermodynamic

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 (Delta H 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.

• 出版日期2008-12-15