title: 3-Aryl-4-acyloxyethoxyfuran-2(5H)-ones as inhibitors of tyrosyl-tRNA synthetase: synthesis, molecular docking and antibacterial evaluation.
abstract: Thirty-eight 3-aryl-4-acyloxyethoxyfuran-2(5H)-ones were designed, prepared and tested for antibacterial activities. Some of them showed significant antibacterial activity against Gram-positive organism, Gram-negative organism and fungus. Out of these compounds, 4-(2-(3-chlorophenylformyloxy)ethoxy)-3-(4-chlorophenyl)furan-2(5H)-one (d40) showed the widest spectrum of activity with MIC50 of 2.0μg/mL against Staphylococcus aureus, 4.3μg/mL against Escherichia coli, 1.5μg/mL against Pseudomonas aeruginosa and 1.2μg/mL against Candida albicans. Our data disclosed that MIC50 values against whole cell bacteria are positive correlation with MIC50 values against tyrosyl-tRNA synthetase. Meanwhile, molecular docking of d40 into S. aureus tyrosyl-tRNA synthetase active site was also performed, and the inhibitor tightly fitting the active site might be an important reason why it has high antimicrobial activity.
authors.affiliation: College of Chemistry and Chemical Engineering, Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Wang
authors.forename: Rui-Cheng
authors.initials: RC
authors.lastname: Deng
authors.forename: Jing-Jun
authors.initials: JJ
authors.lastname: Dong
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Peng
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Gao
authors.forename: Shu-Ting
authors.initials: ST
authors.lastname: Li
authors.forename: Wan-Qiang
authors.initials: WQ
authors.lastname: Lin
authors.forename: Chun-Lei
authors.initials: CL
authors.lastname: Lu
authors.forename: Zhu-Ping
authors.initials: ZP
authors.lastname: Xiao
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D005663:Furans; D014448:Tyrosine-tRNA Ligase; C039281:furan
keywords: 3-Aryl-4-acyloxyethoxyfuran-2(5H)-ones; Antibacterial; Molecular docking; Structure–activity relationship; Tyrosyl-tRNA synthetase