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Information × Registration Number 0220U104298, 0120U101545 , R & D reports Title Bioactivity prediction, synthesis and study of new thiazole-containing compounds as potential anticancer agents. popup.stage_title Head Kobzar Oleksandr L., Кандидат хімічних наук Registration Date 16-12-2020 Organization V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine popup.description2 Antitumor activity of a number of new thiazole-containing rhodanine derivatives was predicted using QSAR models developed by us for prediction of compounds cytotoxicity against human laryngeal Hep-2 cells. Based on the obtained results, potential anticancer compounds were selected for synthesis and in vitro evaluation. The synthesized derivatives of 5-(1,3-thiazol-2-ylmethylene)-2-thioxo-1,3-thiazolidin-4-one, 5-(1,3-thiazol-4-ylmethylene)-2-thioxo-1,3-thiazolidin-4-one, and 5-(1,3-thiazol-5-ylmethylene)-2-thioxo-1,3-thiazolidin-4-one with substituents of different nature in the thiazole ring and in the N-3 position of the rhodanine scaffold were characterized by NMR and chromato-mass spectrometry. It has been demonstrated for the first time the thiazole-containing rhodanine derivatives are inhibitors of glutathione-S-transferases, which have elevated activity in tumor cells. The compounds are able inhibit the activity of enzymes with an IC50 values in the micromolar range. The inhibitory effects of the compounds on the activity of glutathione-S-transferases depend on the nature of the thiazole ring, its substituents, as well as on the nature of the substituent at N-3 position of the rhodanine scaffold. Kinetic studies revealed that thiazole-containing N-alkylcarboxylated rhodanines are mixed inhibitors of the enzyme from equine liver with GSH as a substrate and non-competitive in case of CDNB. Possible binding modes suggest that compound are located between N- and C-terminal domains of one of the subunits of the enzyme dimeric structure that can disrupt its catalytic activity. Product Description popup.authors Hodyna Diana M. Synenko Vitaliy O. popup.nrat_date 2020-12-15 Close