Inhibition activities of natural products on serine proteases.
Proteases play a key role in a variety of pathologies, including cancer, pancreatitis and thrombosis. Low molecular inhibitors can act as drugs to combat these pathologies. Twelve natural phenolic compounds and one alkaloid were evaluated. Quercetin was used as a standard in the in vitro tests on serine proteases (trypsin, thrombin and urokinase). Salicin showed a highly selective effect with a value of IC50 = 11.4 microm for thrombin, suggesting it may be a suitable lead structure for developing thrombin inhibitors and thus for perspective thrombolytics. Interesting results were also observed for hyperoside with IC50 = 8.3 microm for urokinase. The flavonoid skeleton seems to be a suitable structure for investigating urokinase inhibitors as prospective drugs for cancer therapy. A very high inhibitory activity on trypsin was observed for the flavonoid silybin (IC50 = 3.7 microm), indicating a prospective structure on which to base possible polyphenolic trypsin inhibitors.
Jedinák
Andrej
A
Institute of Molecular Physiology and Genetics, Vlárska 5, Bratislava 835 34, Slovakia. andrejjedinak@orangemail.sk
Maliar
Tibor
T
Grancai
Daniel
D
Nagy
Milan
M
D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects / Q000378:metabolism*; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013917:Thrombin / Q000037:antagonists & inhibitors; D014357:Trypsin / Q000187:drug effects / Q000378:metabolism; D014361:Trypsin Inhibitors / Q000737:chemistry / Q000494:pharmacology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors
D001688:Biological Products; D006571:Heterocyclic Compounds; D011084:Polycyclic Aromatic Hydrocarbons; D015842:Serine Proteinase Inhibitors; D014361:Trypsin Inhibitors; D012697:Serine Endopeptidases; D014357:Trypsin; D013917:Thrombin; D014568:Urokinase-Type Plasminogen Activator