Inhibition of pathophysiological proteases with novel quercetin derivatives

Novel quercetin derivatives were prepared to change its physicochemical properties and effects on activity of proteolytic enzymes. For them preparation, the selective protection procedures some of the quercetin hydroxyl groups and acylation of the others with acylchlorides were used. The ability of these compounds to inhibit the activity of serine proteases e.g. trypsin, thrombin, urokinase and elastase was studied. In micromolar range, tested derivatives were the most potent inhibitors of thrombin. There was estimated better inhibition of thrombin for prenylated, acetylated, feruloyl and caffeoyl quercetin esters. Slight inhibitory effect of all quercetin derivatives on elastase was found. Among tested derivatives only diquercetin displayed better inhibiton. Trypsin and urokinase were inhibited by quercetin at comparable level. Slight improvement in inhibitory effect of trypsin and urokinase was seen for chloronaphtoquinone quercetin that revealed enhanced inhibiton of thrombin, too. However, no influence on elastase activity was determined for this compound. Obtained results indicate that certain modifications of quercetin structure could improve its biological properties.