Enantioselective inhibition of the binding of rac‐profens to human serum albumin induced by lithocholate

Abstract

The reversible binding of lithocholate to human serum albumin determines a decrease of the binding of rac-ketoprofen. The process was followed by displacement chromatography using increasing concentrations of the competitor, i.e., lithocholate, in the mobile phase. The inhibition of rac-ketoprofen binding resulting was enantioselective and greater displacement was observed for the (S) enantiomer. The displacement process resulting was competitive in nature, the two enantiomers of ketoprofen binding to the same binding site as the modifier. The investigation was extended to other nonsteroidal antiinflammatory drugs. The enantioselective binding inhibition was larger in the case of rac-naproxen and rac-suprofen with respect to the phenomenon observed in the case of rac-ketoprofen. The difference in circular dichroism spectroscopy was also used to characterize the binding of lithocholate to human serum albumin. This bile acid was proven to bind to site II on human serum albumin. The results, as obtained by displacement chromatography and difference circular dichroism spectroscopy, strongly support the hypothesized role of bile acids in inducing the enantioselective inhibition of ketoprofen binding to human serum albumin in patients suffering from liver diseases.

Characterization of interaction between doxycycline and human serum albumin by capillary electrophoresis‐frontal analysis

“…Warfarin and ketoprofen possess strong binding affinity to HSA and they are known to bind at site I (warfarin) and site II (ketoprofen) [9,28]. Although the individual chiral forms of these two drugs are known to have a slightly different binding to HSA [32], the two enantiomers of each drugs are believed to bind to the same site of HSA [33,34]. Hence, in this study racemic warfarin and racemic ketoprofen were employed as displacement ligands for acquisition of information about the location of doxycycline binding to HSA.…”

Drug affinity to immobilized target bio-polymers by high-performance liquid chromatography and capillary electrophoresis

“…As an example, changes in the concentrations of endogenous factors have been invoked to justify the significant inhibition of the ketoprofen binding in hepatic patients. The use of bile acids as competitors demonstrated a direct competition with profens, the binding inhibition resulting enantioselective [107]. Quite recently, applications have been also reported on the role of metal ions on the affinity of a single drug [108].…”

Drug binding to human serum albumin: Abridged review of results obtained with high‐performance liquid chromatography and circular dichroism

“…This is the case, for example, with arylpropionic acids when lithocholic acid is used as the displacer, with increasing concentrations of lithocholic acid in the mobile phase determining a significant reduction of the retention and an increase of the enantioselectivity. 39,40 A different behavior can be observed when using octanoic acid as the displacer. The presence of small quantities (<0.25 mM) of octanoic acid in the mobile phase results in large (about 80%) decreases in the capacity factors of both the enantiomers of profens like ketoprofen and suprofen.…”

“…Here we summarize selected results obtained by spectroscopic analysis of HSA stereospecific interactions with small ligands, with particular emphasis on diazepam (DZP), a prochiral and widely prescribed benzodiazepine. 21,39,40,52,53 When DZP forms a complex with HSA, its solvent environment undergoes a polarity change, as DZP passes from a water solution into a more apolar binding site on the protein. This effect causes a red shift of the DZP's UV absorption band at low energy, where HSA has virtually no absorption.…”