title: Novel 3-arylfuran-2(5H)-one-fluoroquinolone hybrid: design, synthesis and evaluation as antibacterial agent.
abstract: 3-Arylfuran-2(5H)-one, a novel antibacterial pharmacophore targeting tyrosyl-tRNA synthetase (TyrRS), was hybridized with the clinically used fluoroquinolones to give a series of novel multi-target antimicrobial agents. Thus, twenty seven 3-arylfuran-2(5H)-one-fluoroquinolone hybrids were synthesized and evaluated for their antimicrobial activities. Some of the hybrids exhibited merits from both parents, displaying a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria. The most potent compound (11) in antibacterial assay shows MIC50 of 0.11μg/mL against Multiple drug resistant Escherichia coli, being about 51-fold more potent than ciprofloxacin. The enzyme assays reveal that 11 is a potent multi-target inhibitor with IC50 of 1.15±0.07μM against DNA gyrase and 0.12±0.04μM against TyrRS, respectively. Its excellent inhibitory activities against isolated enzymes and intact cells strongly suggest that 11 deserves to further research as a novel antibiotic.
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wang
authors.affiliation: College of Biology and Environmental Science, Jishou University, Jishou 416000, PR China.
authors.forename: Yun-Tao
authors.initials: YT
authors.lastname: Tang
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Rui-Cheng
authors.initials: RC
authors.lastname: Deng
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Li
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Sha-Sha
authors.initials: SS
authors.lastname: Zhou
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Jing-Wen
authors.initials: JW
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Chemical Engineering, Jishou University, Jishou 416000, 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, Jishou University, Jishou 416000, PR China. Electronic address: oyhmail@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Ouyang
authors.affiliation: College of Chemistry and Chemical Engineering, 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: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects*; D024841:Fluoroquinolones / Q000737:chemistry / Q000494:pharmacology*; D005663:Furans / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D005663:Furans
keywords: 3-Arylfuran-2(5H)-one; DNA gyrase; Fluoroquinolone; Hybrid; Multi-target; TyrRS