Polyphenol compounds belonging to flavonoids inhibit activity of coagulation factor X.
Blood coagulation consists of series of zymogens which can be converted by limited proteolysis to active enzymes leading to the generation of thrombin and conversion of fibrinogen into fibrin by this enzyme. The activated factor X (FXa) forms prothrombinase complex on phosphatidylserine containing surface which is responsible for conversion of prothrombin to thrombin. One molecule of FXa generates more than 1000 thrombin molecules. Therefore FXa is a novel target for modern anticoagulant therapy. The aim of our present study is to examine the effects of the well-known plant polyphenolic compounds on factor Xa amidolytic activity and characterization of these interactions using bioinformatic ligand docking method. We observed that only four polyphenols belonging to flavonoids group: procyanidin B2, cyanidin, quercetin and silybin, had inhibitory effect on FXa activity. Bioinformatic analyses revealed that procyanidin B2, cyanidin, quercetin and silybin bound in the S1-S4 pockets located in vicinity of the FXa active site and blocked access of substrates to Ser195. The results presented here showed that flavonoids might be potential structural bases for design of new nature-based, safe, orally bioavailable direct FXa inhibitors.
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland. Electronic address: mbijak@biol.uni.lodz.pl.
Michal
M
Bijak
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Michal Blazej
MB
Ponczek
Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.
Pawel
P
Nowak
D000577:Amides / Q000378:metabolism; D000595:Amino Acid Sequence; D019295:Computational Biology; D005170:Factor X / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D020128:Inhibitory Concentration 50; D008024:Ligands; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D059808:Polyphenols / Q000378:metabolism / Q000494:pharmacology*; D017434:Protein Structure, Tertiary
D000577:Amides; D008024:Ligands; D059808:Polyphenols; D005170:Factor X
Factor X; Flavonoids; Polyphenolic compounds