Next Article in Journal
Site-Specific PEGylated Adeno-Associated Viruses with Increased Serum Stability and Reduced Immunogenicity
Previous Article in Journal
2,5-Dihydroxyacetophenone Induces Apoptosis of Multiple Myeloma Cells by Regulating the MAPK Activation Pathway
Article Menu
Issue 7 (July) cover image

Export Article

Open AccessArticle
Molecules 2017, 22(7), 1153;

Warfarin and Flavonoids Do Not Share the Same Binding Region in Binding to the IIA Subdomain of Human Serum Albumin

Department of Medicinal Chemistry, University of Zagreb, Faculty of Pharmacy and Biochemistry, Ante Kovačića 1, 10000 Zagreb, Croatia
UMR408 SQPOV, Safety and Quality of Plant Products, INRA, Avignon University, 228 Route de l’Aérodrome, 84000 Avignon, France
Institute of Clinical Laboratory Diagnostics, Osijek University Hospital Center, Josipa Huttlera 4, 31000 Osijek, Croatia
Department of Pharmacology, School of Medicine, University of Osijek, Cara Hadrijana 10/E, 31000 Osijek, Croatia
Author to whom correspondence should be addressed.
Received: 11 June 2017 / Accepted: 7 July 2017 / Published: 11 July 2017
(This article belongs to the Section Natural Products Chemistry)
Full-Text   |   PDF [3863 KB, uploaded 11 July 2017]   |  


Human serum albumin (HSA) binds a variety of xenobiotics, including flavonoids and warfarin. The binding of another ligand to the IIA binding site on HSA can cause warfarin displacement and potentially the 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 eight 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 sites, 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. View Full-Text
Keywords: flavonoids; HSA binding; subdomain IIA; fluorimetry; docking; molecular modeling flavonoids; HSA binding; subdomain IIA; fluorimetry; docking; molecular modeling

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material


Share & Cite This Article

MDPI and ACS Style

Rimac, H.; Dufour, C.; Debeljak, Ž.; Zorc, B.; Bojić, M. Warfarin and Flavonoids Do Not Share the Same Binding Region in Binding to the IIA Subdomain of Human Serum Albumin. Molecules 2017, 22, 1153.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top