Molecular displacement of warfarin from human serum albumin by flavonoid aglycones (CROSBI ID 202035)
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Poór, Miklós ; Li, Yin ; Kunsági-Máté, Sándor ; Petrik, Jozsef ; Vladimir-Knežević, Sanda ; Kőszegi, Tamás
engleski
Molecular displacement of warfarin from human serum albumin by flavonoid aglycones
The well-known 4-hydroxycoumarin derivative warfarin is a widespread anticoagulant drug. Besides its strong albumin binding property warfarin has a narrow therapeutic window. Therefore, a few percent of displacement from albumin can result in serious biological consequences. The flavonoid molecular group also shows very strong plasma albumin binding characteristics occupying the same binding site. It is plausible to hypothesize that flavonoid aglycones may be able to displace warfarin from human serum albumin (HSA). In our study the competing activities of different flavone (acacetin, apigenin, chrysin, luteolin), flavonol (galangin, quercetin) and flavanone (hesperetin, naringenin) aglycones were investigated using fluorescence spectroscopy. Our results represent that flavonoids are able to displace warfarin from the surface of HSA. On the other hand, when comparing flavone or flavonol groups to flavanones the latter group seems to be much weaker competitor. These observations were also supported by calculation of stability constants. Our investigations strongly suggest that we should reckon with the described molecular displacement. However, further in vivo studies are needed to support the findings of our model system.
Flavonoid aglycones; fluorescence spectroscopy; human serum albumin; molecular displacement; warfarin
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