Title |
Synthesis and evaluation of new tyrosyl-tRNA synthetase inhibitors as antibacterial agents based on a N2-(arylacetyl)glycinanilide scaffold
|
---|---|
Published in |
European Journal of Medicinal Chemistry, August 2015
|
DOI | 10.1016/j.ejmech.2015.08.025 |
Pubmed ID | |
Authors |
Zhu-Ping Xiao, Wei Wei, Peng-Fei Wang, Wei-Kang Shi, Na Zhu, Me-Qun Xie, Yu-Wen Sun, Ling-Xia Li, Yong-Xiang Xie, Liang-Song Zhu, Nian Tang, Hui Ouyang, Xian-Hui Li, Guang-Cheng Wang, Hai-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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | 5% |
Unknown | 20 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 3 | 14% |
Student > Ph. D. Student | 3 | 14% |
Student > Master | 2 | 10% |
Lecturer | 1 | 5% |
Other | 1 | 5% |
Other | 3 | 14% |
Unknown | 8 | 38% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 6 | 29% |
Biochemistry, Genetics and Molecular Biology | 4 | 19% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 5% |
Medicine and Dentistry | 1 | 5% |
Computer Science | 1 | 5% |
Other | 0 | 0% |
Unknown | 8 | 38% |