Comparative study of the effects of the structurally similar flavonoids quercetin and taxifolin on the therapeutic behavior of alprazolam

Abstract

After a meal rich in plant products, dietary flavonoids can be detected in plasma as serum albumin bound conjugates. Flavonoid–albumin binding is expected to control the bioavailability of drugs. In this study, the binding of alprazolam (ALP) and human serum albumin (HSA) has been investigated in the absence and presence of two flavonoids with similar structures, quercetin (QUER) and taxifolin (TAX), by means of fluorescence spectroscopy, chemometrics, and molecular dynamics simulation. Our results show that ALP has the ability to quench the intrinsic fluorescence of HSA. This quenching is affected by flavonoids. The presence of QUER and TAX decreased the quenching constants, binding constants, and equilibrium constants associated with ALP binding to HSA. The effect of ALP and both flavonoids on the conformation of HSA was analyzed using synchronous fluorescence spectroscopy. Our results indicate a conformational change of HSA with the addition of ligands. The molecular dynamics study makes an important contribution to understanding the effect of the binding of ALP, QUER, and TAX on conformational changes of HSA and modification of its tertiary structure in the absence and presence of flavonoids. All of these results may have relevant consequences in rationalizing the interferences of common food and drugs.