Scope of this project is the study inhibition of cyclooxygenases (COXs) and lipoxygenases (LOXs) enzymes by plant quinones. COXs and LOXs play key role in regulation of inflammatory diseases, in growth of cancer cells and in other pathological processes in mammalian tissues. Therefore currant research is aimed on searching for dual inhibitors of COX-2 and 5-LOX enzymes. Plant compounds are served as prospective source of these compounds. In vitro enzyme assay monitoring production of prostaglandins and leukotrienes which are products of COX and LOX pathway respectively will be used for tests. Screening of selected plant quinones for COX-1, COX-2 and 5-LOX inhibition and impact of simple derivatization steps on its activity will be carried out during the project solving. For perspective compounds inhibitory concentrations (IC50) will established and selectivity for enzymes will be calculated. Most active compounds will be tested for its toxicity. Moreover, study of mechanism of inhibition will be performed for selected constituents. (en)
Cílem projektu je nalezení látek efektivně inhibujících současně COX-2 a 5-LOX, které by mohly sloužit pro vývoj nových bezpečných protizánětlivých léků. Dalším cílem je ověřit vliv jednoduchých derivatizací chinonů na jejich inhibiční aktivitu. U aktivních látek zjištění způsobu inhibice enzymů.