Structural and electronic determinants of flavonoid binding to human serum albumin: an extensive ligand-based study

Rimac, Hrvoje; Debeljak, Željko; Šakić, Davor; Weitner, Tin; Gabričević, Mario; Vrček, Valerije; Zorc, Branka; Bojić, Mirza

doi:10.1039/c6ra17796d

Cited by 15 publications

(24 citation statements)

References 67 publications

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“…[ 35 ] Additionally, docking of ( R )- and ( S )-warfarin was also performed in presence of crystallized ( R )-warfarin to locate a putative secondary binding site located in Sudlow’s site I. The three-dimensional forms of the ligands were drawn and their initial geometries were optimized in HyperChem 8.0 (Hypercube, Inc., Gainesville, FL, USA), and their charge was set to represent the most abundant species at pH 7.4, calculated according to Rimac et al [ 48 ], as well as verified at chemicalize.com. For ( R )- and ( S )-warfarin, anionic species were docked, while for quercetin and quercetin-3- O -glucuronide, two most prevalent anionic and fluorescent species [ 49 ] were docked.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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“…3 Investigation of avonoids from dietary sources has attracted considerable interest because of their nutritional and medical effects in humans. Most of their bioactivity is related to their structure; 4,5 for example, the presence of a 2,3 double bond in conjugation with a 4-oxo group and a catechol unit (1,2-dihydroxybenzene) is usually required for antioxidant activity in avonoids. Methylation, hydroxylation, and glycosylation of avonoids also affect their absorption, metabolism, and bioactivities in vivo.…”

Section: Introductionmentioning

confidence: 99%

The interaction of dietary flavonoids with xanthine oxidase in vitro: molecular property-binding affinity relationship aspects

et al. 2019

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“…Three homologous domains (domains I–III), in turn divided into two subdomains (A and B), with multiple ligand-binding sites localized in each of these subdomains were described [ 20 , 25 ]. Many drugs bind to one of the two primary binding sites located in subdomains IIA and IIIA (Sudlow sites I and II, respectively) [ 26 ]. As the most prominent one, the IIA subdomain appears to be spacious.…”

Section: Introductionmentioning

confidence: 99%

“…Binding of flavonoids to HSA was extensively studied using different fluorescence spectroscopy techniques [ 29 , 30 , 31 , 32 , 33 ]. The observed change in fluorescence enables the calculation of HSA-ligand complexes stability constants and also the distance between the ligand and Trp 214 [ 26 ]. Many studies reported the binding between flavonoids and serum albumins [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Structure–Affinity Relationship of Flavonoids in Lotus Leaf (Nelumbo nucifera Gaertn.) on Binding to Human Serum Albumin and Bovine Serum Albumin by Spectroscopic Method

Tang

Liu

2017

Molecules

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Lotus leaf has gained growing popularity as an ingredient in herbal formulations due to its various activities. As main functional components of lotus leaf, the difference in structure of flavonoids affected their binding properties and activities. In this paper, the existence of 11 flavonoids in lotus leaf extract was confirmed by High Performance Liquid Chromatography (HPLC) analysis and 11 flavonoids showed various contents in lotus leaf. The interactions between lotus leaf extract and two kinds of serum albumins (human serum albumin (HSA) and bovine serum albumin (BSA)) were investigated by spectroscopic methods. Based on the fluorescence quenching, the interactions between these flavonoids and serum albumins were further checked in detail. The relationship between the molecular properties of flavonoids and their affinities for serum albumins were analyzed and compared. The hydroxylation on 3 and 3’ position increased the affinities for serum albumins. Moreover, both of the methylation on 3’ position of quercetin and the C2=C3 double bond of apigenin and quercetin decreased the affinities for HSA and BSA. The glycosylation lowered the affinities for HSA and BSA depending on the type of sugar moiety. It revealed that the hydrogen bond force played an important role in binding flavonoids to HSA and BSA.

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Structural and electronic determinants of flavonoid binding to human serum albumin: an extensive ligand-based study

Abstract: The most prominent features responsible for binding of flavonoid aglycones to the IIA region of human serum albumin (HSA) were determined based onin vitrofluorescence measurements and density functional theory calculations.

Cited by 15 publications

References 67 publications

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

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

The interaction of dietary flavonoids with xanthine oxidase in vitro: molecular property-binding affinity relationship aspects

Molecular Structure–Affinity Relationship of Flavonoids in Lotus Leaf (Nelumbo nucifera Gaertn.) on Binding to Human Serum Albumin and Bovine Serum Albumin by Spectroscopic Method

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