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Information × Registration Number 0221U106932, 0120U000079 , R & D reports Title Multitarget drug discovery against Staphylococcus aureus and development of fluorescent assay to evaluate antibiofilm activity for identified antibacterial agents popup.stage_title Head Volynets Halyna P., Кандидат біологічних наук Registration Date 22-12-2021 Organization Institute of Molecular Biology and Genetics of NAS of Ukraine popup.description2  In the course of the Project, recombinant Staphylococcus aureus threonyl-tRNA synthetase (ThrRS) and seryl-tRNA synthetase (SerRS) were obtained. We have performed molecular docking of compound collection containing 124,830 ligands into active sites of S. aureus ThrRS and SerRS and selected 180 compounds for investigation of their inhibitory activity toward recombinant enzymes in aminoacylation assay. Among the tested compounds, we identified five inhibitors from different chemical classes decreasing the activity of ThrRS by more than 70% at a concentration of 100 μM. The most active compound 2,4-dibromo-6-{[4-(4-nitro-phenyl)-thiazol-2-yl]-hydrazonomethyl}-phenol has an IC50 value of 56.5 ± 3.5 μM. These compounds are not cytotoxic toward eukaryotic cells HEK293 (EC50 > 100 μM). Also, according to the results of biological screening we have found that compounds belonging to three chemical classes – derivatives of 2-(benzothiazol-2-ylsulfanyl)-1-phenyl-ethanone, 4-phenyl-2-propionylamino-thiophene-3-carboxylic acid ethyl ester and N-benzylidene-N’-(4-phenyl-thiazol-2-yl)-hydrazine are able to inhibit activity simultaneously of both enzymes – S. aureus ThrRS and SerRS. It was found that compound 3-[N’-(2,3-dimethoxy-benzylidene)-hydrazino]-6-methyl-4H-[1,2,4]triazin-5-one possesses antibacterial activity toward S. aureus in planktonic and biofilm forms with MIC value of 32 mg/l and does not reveal antibacterial effect toward gram-negative bacteria Escherichia coli. During Project realization we have developed three fluorescent dyes – Dye-51, Dye-66 and Dye 16, for visualization of biofilm amyloid components in S. aureus. Product Description popup.authors popup.nrat_date 2021-12-22 Close