title: Thrombin inhibitory activity of some polyphenolic compounds.
abstract: Thrombin, also known as an active plasma coagulation factor II, belongs to the family of serine proteases and plays a crucial role in blood coagulation process. The process of thrombin generation is the central event of the hemostatic process and regulates blood coagulant activity. For this reason, thrombin inhibition is key to successful novel antithrombotic pharmacotherapy. The aim of our present study was to examine the effects of the well-known polyphenolic compounds on the activity of thrombin, by characterization of its interaction with selected polyphenols using different biochemical methods and biosensor BIAcore analyses. Only six compounds, cyanidin, quercetin, silybin, cyanin, (+)-catechin and (-)-epicatechin, of all examined in this study polyphenols caused the inhibition of thrombin amidolytic activity. But only three of the six compounds (cyanidin, quercetin and silybin) changed thrombin proteolytic activity. BIAcore analyses demonstrated that cyanidin and quercetin caused a strong response in the interaction with immobilized thrombin, while cyanin and (-)-epicatechin induced a low response. Lineweaver-Burk curves show that used polyphenol aglycones act as competitive thrombin inhibitors. Our results suggest that polyphenolic compounds might be potential structural bases and source to find and project nature-based, safe, orally bioavailable direct thrombin inhibitors.
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Bijak
authors.affiliation: Organic and Pharmaceutical Technology Group, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 29, 50-370 Wroclaw, Poland.
authors.forename: R
authors.initials: R
authors.lastname: Ziewiecki
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Saluk
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Ponczek
authors.affiliation: Organic and Pharmaceutical Technology Group, Faculty of Chemistry, Wroclaw University of Technology, Wybrzeze Wyspianskiego 29, 50-370 Wroclaw, Poland.
authors.forename: I
authors.initials: I
authors.lastname: Pawlaczyk
authors.affiliation: Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wroclaw, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Krotkiewski
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: B
authors.initials: B
authors.lastname: Wachowicz
authors.affiliation: Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
authors.forename: P
authors.initials: P
authors.lastname: Nowak
keywords: Flavonoids; Inhibition; Polyphenolic compounds; Proteolytic activity; Thrombin