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.
Proteases play a regulatory role in a variety of pathologies including cancer, pancreatitis, thromboembolic disorders, viral infections and many others. One of the possible strategies how to combat with these pathologies seems to be the use of low molecular inhibitors. Natural products were evaluated in the in vitro antiprotease assay on serine proteases (trypsin, thrombin and urokinase) and on the cysteine protease cathepsin B. We found interesting results for -ursolic acid isolated from Salvia officinalis, which significantly inhibited all tested proteases in vitro in the micromolar range. -Ursolic acid showed the strongest inhibition activity to urokinase (IC 50 = 12 μm) and cathepsin B (IC 50 = 10 μm) as proteases included in tumour invasion and metastasis indicated possible anticancer effectivity. Therefore, we tested the ability of -ursolic acid at doses of 50, 75 and 100 mg/kg given i.p. to inhibit lung colonization of B16 mouse melanoma cells in vivo. We found, that -ursolic acid significantly decreased the number of B16 colonies in the lungs of mice at the dose 50 mg/kg (p Ͻ 0.05).
The rye flour is, together with the wheat flour, the basic ingredient used in traditional bread baking. The rye grain contains many compounds with significant impacts on the consumer. Considering that, various biologically active phytochemicals were determined in extracts from mature grains of 19 rye genotypes (Secale cereale L.). The content of total phenols, flavonoids, phenolic acids and thiols, as well as antioxidant activities and inhibitory activities against trypsin, thrombin, and urokinase were analyzed by spectrophotometric methods. The vanillic acid, vanillin, p-coumaric acid, and t-ferulic acid were analyzed in particular by high performance liquid chromatography (HPLC). The observed differences in the amounts and activities between rye genotypes reflected variations in their genetic background. Rye grain is a remarkable source of specific phytochemicals. Genetic diversity in rye makes it possible to identify individual genotypes that have a unique content and biological activity of compounds deposited in mature grains. One subgroup of rye genotypes had higher values of antioxidant properties and concentrations of polyphenols. Other sub-group had higher proteinase inhibitory activities and contents of polyphenols. The third sub-group contained as though the universal genotypes, i.e. genotypes with average values in nearly all the measured parameters.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.