title: Synthesis and evaluation of new tyrosyl-tRNA synthetase inhibitors as antibacterial agents based on a N2-(arylacetyl)glycinanilide scaffold.
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.
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: xiaozhuping2005@163.com.
authors: Zhu-Ping
authors: ZP
authors: Xiao
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Wei
authors: W
authors: Wei
authors: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors: Peng-Fei
authors: PF
authors: Wang
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Wei-Kang
authors: WK
authors: Shi
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Na
authors: N
authors: Zhu
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Me-Qun
authors: MQ
authors: Xie
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Yu-Wen
authors: YW
authors: Sun
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Ling-Xia
authors: LX
authors: Li
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Yong-Xiang
authors: YX
authors: Xie
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Liang-Song
authors: LS
authors: Zhu
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Nian
authors: N
authors: Tang
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China. Electronic address: oyhmail@163.com.
authors: Hui
authors: H
authors: Ouyang
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Xian-Hui
authors: XH
authors: Li
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors: Guang-Cheng
authors: GC
authors: Wang
authors: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: zhuhl@nju.edu.cn.
authors: Hai-Liang
authors: HL
authors: Zhu
mesh_terms: D000083:Acetanilides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D044482:Benzeneacetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000083:Acetanilides; D000900:Anti-Bacterial Agents; D044482:Benzeneacetamides; D004791:Enzyme Inhibitors; C000608202:N2-((3-chlorophenyl)acetyl)-N-(4-nitrophenyl)glycinamide; D014448:Tyrosine-tRNA Ligase
keywords: Antibacterial agent; Molecular docking; N2-(arylacetyl)glycinanilide; Structure–activity relationship; TyrRS inhibitor