Flavonoids inhibit the amidolytic activity of human thrombin.
The effect of a group of natural flavonoids on human thrombin amidolytic activity was investigated using a spectrophotometric inhibition assay while information on the kinetics and thermodynamics was obtained using optical biosensor techniques. All the flavonoids tested acted as reversible inhibitors, and the quercetin-thrombin complex was found to be most stable at pH=7.5. Docking analysis indicated that quercetin's inhibitory behavior could be related to its planar structure and low steric hindrance, and to its ability to form a critical H-bond with thrombin His57.
Mozzicafreddo
M
M
MCAB Department, University of Camerino, Camerino, MC, Italy. matteo.mozzicafreddo@unicam.it
Cuccioloni
M
M
Eleuteri
A M
AM
Fioretti
E
E
Angeletti
M
M
D000581:Amidohydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry; D001120:Arginine / Q000031:analogs & derivatives; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive; D015374:Biosensing Techniques; D001777:Blood Coagulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004795:Enzyme Stability; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D010875:Pipecolic Acids / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D005419:Flavonoids; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; D000581:Amidohydrolases; C031942:argatroban