Search academic texts

Information × Registration Number 0222U005338, 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 27-12-2022 Organization V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine popup.description2  The inhibitory activity of new hydrogen-containing derivatives of nitrogenous heterocycles against xanthine oxidase was predicted. For this purpose, computer screening of a number of virtual structures using molecular docking was carried out. Based on the obtained results, 20 compounds with potential inhibitory ability against xanthine oxidase were selected for their further synthesis and in vitro evaluation. Derivatives of 4-(2-(5-Oxo-1,5-dihydro-4H-pyrazol-4-ylidene)hydrazinyl)benzenesulfonamide and (Z)-4-(2-(5-Oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)hydrazinyl)benzoic acid with different moieties in the first and third positions of the pyrazolone fragment were synthesized. The structures of the synthesized compounds were characterized by 1H NMR and 13C NMR spectroscopy, as well as chromatography-mass spectrometry. It was demonstrated in vitro that hydrozone-containing derivatives of nitrogenous heterocycles are capable of inhibiting xanthine oxidase, the increased activity of which is associated with hyperuricemia along with correlated diseases, including cardiovascular diseases, kidney diseases, etc. The compounds were shown to inhibit enzyme activity in the micromolar range of IC50 values. At the same time, the inhibitory effect of the compounds on the activity of xanthine oxidase depended on the chemical nature of the pyrazolone ring residues, as well as on the position of the carboxylic acid moiety of the heterocycle molecule. According to the results of kinetic studies, hydrogen-containing derivatives of nitrogenous heterocycles are mixed inhibitors of xanthine oxidase. Product Description popup.authors Kachaeva Maryna V. Tatarchuk Alʹona V. popup.nrat_date 2022-12-27 Close