title: Synthesis and evaluation of adenosine containing 3-arylfuran-2(5H)-ones as tyrosyl-tRNA synthetase inhibitors.
abstract: Tyrosyl-tRNA synthetase (TyrRS) is an aminoacyl-tRNA synthetase family protein that possesses an essential role in bacterial protein synthesis. The synthesis, structure-activity relationship, and evolution of a novel series of adenosine-containing 3-arylfuran-2(5H)-ones as TyrRS inhibitors are described. Advanced compound d3 from this series exhibited excellent affinity for TyrRS with IC50of 0.61 ± 0.04 μM. Bacterial growth inhibition assays demonstrated that d3 showed submicromolar antibacterial potency against Escherichia coli and Pseudomonas aeruginosa, and compared to the marketed antibiotics ciprofloxacin.
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China; College of Chemistry and Chemical Engineering, Sichuan University of Arts and Science, Dazhou 635000, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Zhen-Zhen
authors.initials: ZZ
authors.lastname: Li
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Wei-Kang
authors.initials: WK
authors.lastname: Shi
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Xiao-Cong
authors.initials: XC
authors.lastname: Wang
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Xu
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Li
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China.
authors.forename: Fu-Rui
authors.initials: FR
authors.lastname: Jiang
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, Jishou University, Jishou 416000, PR China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: xiaozhuping2005@163.com.
authors.forename: Zhu-Ping
authors.initials: ZP
authors.lastname: Xiao
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan Engineering Laboratory for Analyse and Drugs Development of Ethnomedicine in Wuling Mountains, 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.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D004927:Escherichia coli Infections / Q000188:drug therapy; D006367:HeLa Cells; D006801:Humans; D062105:Molecular Docking Simulation; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology*; D013329:Structure-Activity Relationship; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D014448:Tyrosine-tRNA Ligase; D000241:Adenosine
keywords: 3-Arylfuran-2(5H)-one; Adenosine; Antibacterial; Molecular docking; Tyrosyl-tRNA synthetase inhibitors