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Tyrosyl-tRNA synthetase inhibitors as antibacterial agents: synthesis, molecular docking and structure-activity relationship analysis of 3-aryl-4-arylaminofuran-2(5H)-ones |
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| Authors: | Xiao Zhu-Ping Ma Tao-Wu Liao Mei-Lin Feng Yu-Ting Peng Xiao-Chun Li Jia-Liang Li Zhi-Ping Wu Ying Luo Qun Deng Yang Liang Xiao Zhu Hai-Liang |
| Affiliation: | a Key Laboratory of Plant Resources Conservation and Utilization, College of Hunan Province, Jishou University, Jishou 416000, PR China b Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou 416000, PR China c Key Laboratory of Ecotourism’s Application Technology, Hunan Province, Jishou University, Jishou 416000, PR China d College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China e State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China |
| Abstract: | Thirty-five 3-aryl-4-arylaminofuran-2(5H)-one derivatives were designed, prepared and tested for their inhibitory activity against tyrosyl-tRNA synthetase. Out of these compounds, 3-(3-bromophenyl)-4-(3,5-dichlorophenylamino)furan-2(5H)-one (35) was the most active with IC50 of 0.09 ± 0.02 μM. The structure-activity relationship revealed that introduction of chlorine atoms at both meta positions of aniline moiety significantly increased the enzyme inhibitory activity. The results of antibacterial assay revealed that the tested compounds showed good activity against Gram-positive bacteria, with 35 being the most potent with MIC50 of 0.06 μg/mL against Staphylococcus aureus ATCC 25923. Molecular docking of 35 into S. aureus tyrosyl-tRNA synthetase active site was also performed. The inhibitor snugly fitting the active site may well explain its excellent inhibitory activity. |
| Keywords: | 3-Aryl-4-arylaminofuran-2(5H)-one Antibacterial agent Molecular docking Tyrosyl-tRNA synthetase Structure-activity relationship |
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