Work

The aim of the project is the search, synthesis and study of new hydrazone-containing derivatives of nitrogenous heterocycles as potential inhibitors of purine metabolism. The overall research plan includes prediction of inhibitory potential by means of virtual screening. Promising compounds that can demonstrate inhibitory ability will be synthesized and characterized by elemental analysis, NMR, IR and mass spectroscopy. Evaluation of the inhibitory ability and kinetic parameters of the synthesized compounds will be performed in a model system in vitro using the enzyme preparation of xanthine oxidase and its substrate - xanthine. The first stage (July 1, 2021- December 31, 2021) ) will include work with a database of virtual chemical structures to establish the theoretical basis for the construction of new hydrazone-containing derivatives of nitrogenous heterocycles as xanthine oxidase inhibitors. This involves virtual screening by molecular docking using crystallographic structures of xanthine oxidase. The compounds thus identified as potential inhibitors of the enzyme will be synthesized and studied in a model system in vitro. The second stage (January 1, 2022 - December 31, 2022) will include expanding the working database of chemical structures in view of the found theoretical aspects of the xanthine oxidase inhibition. Molecular docking approach will be used to optimize the structures, which will improve the inhibitory effect. The synthesized compounds will be characterized and tested in vitro. As a result, for the first time new diazo compounds will be studied as inhibitors of xanthine oxidase. The inhibitory potential of these compounds will be characterized using kinetic approaches. Computer models will be developed to provide an understanding of bioorganic mechanisms and further target-oriented search for promising compounds.