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Pregled bibliografske jedinice broj: 788931

Interactions of Warfarin with Quercetin and Luteolin Analogs in Binding to HSA

Rimac, Hrvoje; Dufour, Claire; Debeljak, Željko; Bojić, Mirza; Zorc, Branka
Interactions of Warfarin with Quercetin and Luteolin Analogs in Binding to HSA // Proceedings of PhD Student Poster Session
Urbino: European Federation for Medicinal Chemistry, 2015. str. 68-69 (poster, međunarodna recenzija, sažetak, znanstveni)

Interactions of Warfarin with Quercetin and Luteolin Analogs in Binding to HSA

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

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Proceedings of PhD Student Poster Session / - Urbino : European Federation for Medicinal Chemistry, 2015, 68-69

European School for Medicinal Chemistry (XXXV Advanced Course of Medicinal Chemistry) and "E. Duranti" National Seminar for PhD Students

Mjesto i datum
Urbino, Italija, 28.6.-3.7.2015.

Vrsta sudjelovanja

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Quercetin; luteolin; warfarin; HSA; interactions

Background: Flavonoids are a diverse group of natural products, derivatives of 2- or 3- phenyl-, 4-benzopyrone, which are highly present in human diet via fruits and vegetables. They also show a wide range of pharmacological effects, such as cardioprotective, antiinflamatory and antioxidative effects. Upon entering circulation, flavonoids bind primarily to the IIA binding site of human serum albumin (HSA)2, where a significant number of drugs can also be bound. These can lead to interactions and increase of free drug concentration in blood. Aims: The aim of this work is to better understand binding properties of the IIA binding region of HSA and to investigate warfarin-flavonoid interactions in HSA binding. This can lead to optimization of drug dosage regimes in order to avoid drug adverse effects. Methods: Binding of warfarin and quercetin and luteolin analogs to the IIA binding region was investigated by observing quenching of the tryptophan fluorescence, which is located in the aforementioned binding site (λabs = 295 nm, λem = 320 nm)2. Additionally, HSA was preincubated with warfarin in order to achieve a certain percentage of the binding site saturation (0%, 30%, 50%, 75% and 96%). Afterwards, investigated flavonoids were added to the mixture and the interaction was measured by observing increase in fluorescence intensity of flavonoids which occurs when they are bound to HSA (λabs = 450 nm, λem = 526 nm). Results: Quenching of tryptophan fluorescence data show that all of the investigated flavonoids (quercetin, quercetin-3-O-glucuronide, quercetin-3-O-glucoside (isoquercitrin), quercetin-3-O-galactoside (hyperoside), quercetin-3-O-rhamnoglucoside (rutin), luteolin, luteolin-6-C-glucoside (isooorientin) andluteolin-7-O-glucoside (cynaroside), as well as warfarin bind in the same IIA binding region of HSA Data acquired from binding of investigated flavonoids to warfarin- preincubated HSA show that binding of warfarin has significant influence on fluorescence intensity of bound flavonoids, especially at higher percentage of occupied sites, but has very little effect on the flavonoid concentration needed to achieve the fluorescence maximum. This can be explained by conformational changes that HSA undergoes after warfarin binding. This subsequently changes the conformation of the bound flavonoid to a less flourescent conformation, but does not influence flavonoid binding constants. Conclusion: Even though warfarin and investigated flavonoids bind in the same binding region of HSA, their exact binding site is not identical and therefore do not enter any significant pharmacokinetic interactions. Most of the variance in fluorescence intensity data can be explained by conformational changes of HSA and flavonoids to their less fluorescent conformation.

Izvorni jezik

Znanstvena područja
Kemija, Farmacija


Farmaceutsko-biokemijski fakultet, Zagreb,
Klinički bolnički centar Osijek