Search academic texts

Information × Registration Number 0221U106619, 0121U111935 , R & D reports Title New hydrazone-containing derivatives of nitrogen heterocycles as potential inhibitors of purine metabolism popup.stage_title Head Buldenko Vladyslav M., к.х.н. Registration Date 16-12-2021 Organization V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine popup.description2  Statistics show that the prevalence and incidence of hyperuricemia in different countries ranges from 8% to 40% among the adult population and continues to grow. According to a 2007-2008 study, 3.9% of the US population over the age of 20 is already diagnosed with gout, and hyperuricemia occurs in 21% of the population. The prevalence of gout in Europe is up to 4%. At the same time, the number of cases of hyperuricemia and gout has been increasing worldwide up to 2 times per decade. A number of side effects of known drugs as well as a number of compounds with xanthine oxidase inhibitory activity indicate the relevance and need to continue the search for new enzyme inhibitors. Therefore, the main purpose of this work is to establish theoretical aspects of the design of new hydrazone-containing derivatives of nitrogen heterocycles as xanthine oxidase inhibitors. To achieve this goal, a database of virtual hydrazone-containing derivatives of nitrogen heterocycles was developed and computer screening was performed using molecular docking. Based on the obtained data, 10 compounds were selected for synthesis and in vitro testing. New hydrazone-containing heterocycles were synthesized by azocoupling of diazonium salts of para- and meta-aminobenzoic acid and esters of acetoacetic acid and substituted pyrazolones. Their structures were characterized by 1H and 13C NMR, as well as by chromato-mass spectrometry. The in vitro ability of the synthesized compounds to inhibit xanthine oxidase activity was evaluated. Two promising compounds for further research and structural optimization have been identified. It was found that the most active hydrazone-containing derivatives with a pyrazolone moiety inhibit xanthine oxidase activity in accordance with mixed type of inhibition mechanism. Product Description popup.authors Kachaeva Maryna V. Tatarchuk Alʹona V. popup.nrat_date 2021-12-16 Close