Naslov
Warfarin and flavonoids do not share the same binding region in binding to the IIA subdomain of human serum albumin

Autori
Rimac, Hrvoje ; Dufour, Claire ; Debeljak, Željko ; Zorc, Branka ; Bojić, Mirza

Izvornik
Molecules (1420-3049) 22 (2017), 7; 1153-1

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Flavonoids ; HSA binding ; subdomain IIA ; fluorimetry ; docking ; molecular modeling

Sažetak
Human serum albumin (HSA) binds a variety of xenobiotics, including flavonoids and warfarin. Binding of another ligand to the IIA binding site on HSA can cause warfarin displacement and potentially elevation of its free concentration in blood. Studies dealing with flavonoid- induced warfarin displacement from HSA provided controversial results: estimated risk of displacement ranged from none to serious. To resolve these controversies, in vitro study of simultaneous binding of warfarin and 8 different flavonoid aglycons and glycosides to HSA was carried out by fluorescence spectroscopy as well as molecular docking. Results show that warfarin and flavonoids do not share the same binding region in binding to HSA. Interactions were only observed at high warfarin concentrations, not attainable under recommended dosing regimes. Docking experiments show that flavonoid aglycons and glycosides do not bind at warfarin high affinity site, but rather to different regions within the IIA HSA subdomain. Thus, the risk of clinically significant warfarin–flavonoid interaction in binding to HSA should be regarded as negligible.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA