Rational Design of Hit Compounds TargetingStaphylococcus aureusThreonyl-tRNA Synthetase

Mariia Yu Rybak, Olga I. Gudzera, Oksana B. Gorbatiuk, Mariia O. Usenko, Sergiy M. Yarmoluk, Michael A. Tukalo, Galyna P. Volynets

Research output: Contribution to journalArticlepeer-review


Staphylococcus aureusis one of the most dangerous nosocomial pathogens which cause a wide variety of hospital-acquired infectious diseases.S. aureusis considered as a superbug due to the development of multidrug resistance to all current therapeutic regimens. Therefore, the discovery of antibiotics with novel mechanisms of action to combat staphylococcal infections is of high priority for modern medicinal chemistry. Nowadays, aminoacyl-tRNA synthetases are considered as promising molecular targets for antibiotic development. In the present study, we used for the first timeS. aureusthreonyl-tRNA synthetase (ThrRS) as a molecular target. RecombinantS. aureusThrRS was obtained in the soluble form in a sufficient amount for inhibitor screening assay. Using the molecular docking approach, we selected 180 compounds for investigation of inhibitory activity toward ThrRS. 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 IC50value of 56.5 ± 3.5 μM. These compounds are not cytotoxic toward eukaryotic cells HEK293 (EC50> 100 μM) and can be useful for further optimization and biological research.

Original languageEnglish (US)
Pages (from-to)24910-24918
Number of pages9
JournalACS Omega
Issue number38
StatePublished - Sep 28 2021
Externally publishedYes

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering


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