title: Synthesis, structure, molecular docking, and structure-activity relationship analysis of enamines: 3-aryl-4-alkylaminofuran-2(5H)-ones as potential antibacterials.
abstract: Thirty-one 3-aryl-4-alkylaminofuran-2(5H)-ones were designed, prepared and tested for their antibacterial activity. Some of them showed significant antibacterial activity against Gram-positive organisms, especially against Staphylococcus aureus ATCC 25923, but all were inactive against Gram-negative organisms. Out of these compounds, 3-(4-bromophenyl)-4-(2-(4-nitrophenyl)hydrazinyl)furan-2(5H)-one (4a11) showed the most potent antibacterial activity against S. aureus ATCC 25923 with MIC(50) of 0.42 μg/mL. The enzyme assay revealed that the possible antibacterial mechanism of the synthetic compounds might be due to their inhibitory activity against tyrosyl-tRNA synthetase. Molecular dockings of 4a11 into S. aureus tyrosyl-tRNA synthetase active site were also performed. This inhibitor snugly fitting the active site might well explain its excellent inhibitory activity. Meanwhile, this modeling disclosed that a more suitable optimization strategy might be to modify the benzene ring at 3-position of furanone with hydrophilic groups.
authors.affiliation: College of Chemistry and Chemical Engineering, 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: Xing-Bing
authors.initials: XB
authors.lastname: He
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Peng
authors.forename: Tao-Ju
authors.initials: TJ
authors.lastname: Xiong
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Chen
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D009574:Nitro Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors / Q000187:drug effects
chemical_list: C558703:3-(4-bromophenyl)-4-(2-(4-nitrophenyl)hydrazinyl)furan-2(5H)-one; D000588:Amines; D000900:Anti-Bacterial Agents; D005663:Furans; D009574:Nitro Compounds; D014448:Tyrosine-tRNA Ligase