title: 4-alkoxy-3-arylfuran-2(5H)-ones as inhibitors of tyrosyl-tRNA synthetase: synthesis, molecular docking and antibacterial evaluation.
abstract: A series of novel 4-alkoxy-3-arylfuran-2(5H)-ones as tyrosyl-tRNA synthetase inhibitors were synthesized. Of these compounds, 3-(4-hydroxyphenyl)-4-(2-morpholinoethoxy)furan-2(5H)-one (27) was the most potent. The binding model and structure-activity relationship indicate that replacement of morpholine-ring in the side chain of 27 with a substituent containing more hydrophilic groups would be more suitable for further modification. Antibacterial assay revealed that the synthetic compounds are effective against growth of Gram-positive organisms, and 27 is the most potent agent against Staphylococcus aureus ATCC 25923 with MIC(50) value of 0.23 μg/mL.
authors.affiliation: College of Chemistry & Chemical Engineering, and Key Laboratory of Hunan Forest Products and Chemical Industry Engineering, Jishou University, Jishou, PR China. xiaozhuping2005@163.com
authors.forename: Zhu-Ping
authors.initials: ZP
authors.lastname: Xiao
authors.forename: Hui
authors.initials: H
authors.lastname: Ouyang
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Wang
authors.forename: Peng-Cheng
authors.initials: PC
authors.lastname: Lv
authors.forename: Ze-Jun
authors.initials: ZJ
authors.lastname: Huang
authors.forename: She-Rong
authors.initials: SR
authors.lastname: Yu
authors.forename: Tian-Fang
authors.initials: TF
authors.lastname: Yi
authors.forename: Ye-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009025:Morpholines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C561754:3-(4-hydroxyphenyl)-4-(2-morpholinoethoxy)furan-2(5H)-one; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D005663:Furans; D009025:Morpholines; D014448:Tyrosine-tRNA Ligase; D015107:4-Butyrolactone; C039281:furan