Synthesis and evaluation of new tyrosyl-tRNA synthetase inhibitors as antibacterial agents based on a N2-(arylacetyl)glycinanilide scaffold

European Journal of Medicinal Chemistry
Zhu-Ping XiaoHai-Liang Zhu

Abstract

Tyrosyl-tRNA synthetase (TyrRS), an essential enzyme in bacterial protein biosynthesis, is an attractive therapeutic target for finding novel antibacterial agents, and a series of N2-(arylacetyl)glycinanilides has been herein synthesized and identified as TyrRS inhibitors. These efforts yielded several compounds, with IC50 in the low micromolar range against TyrRS from Staphylococcus aureus. Out of the obtained compounds, 3ap is the most active and exhibits excellent activity against both Gram-positive (S. aureus) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains. In comparison with the parent scaffold 3-arylfuran-2(5H)-one, N2-(arylacetyl)glycinanilide significantly improved the potency against Gram-negative bacterial strains, indicating that this scaffold offers a significant potential for developing new antibacterial drugs.

References

Aug 18, 2009·Journal of Bacteriology·Pieter Van de VijverKonstantin Severinov
Oct 3, 2014·Molecular BioSystems·Aleksandra MaršavelskiSanja Tomić

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Citations

Oct 30, 2016·Journal of Biomolecular Structure & Dynamics·Vladyslav O KravchukAlexander I Kornelyuk
Dec 16, 2016·Expert Opinion on Therapeutic Patents·Juan SunHai-Liang Zhu

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