title: Design, synthesis, antibacterial evaluation and docking study of novel 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolone.
abstract: A novel series of 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolones 6a-o were synthesized and evaluated for their in vitro antibacterial activity. Most of the target compounds exhibited potent activity against Gram-positive strains. Among them, moxifloxacin analog 6n displayed the most potent activity against Gram-positive strains including S. epidermidis (MIC = 0.06 μg/mL), MSSE (MIC = 0.125 μg/mL), MRSE (MIC = 0.03 μg/mL), S. aureus (MIC = 0.125 μg/mL), MSSA (MIC = 0.125 μg/mL), (MIC = 2 μg/mL). Its activity against MRSA was eightfold more potent than reference drug gatifloxacin. Finally, docking study of the target compound 6n revealed that the binding model of quinolone nucleus was similar to that of gatifloxacin and the 2-hydroxy-3-(nitroimidazolyl)-propyl group formed two additional hydrogen bonds.
authors.affiliation: Center of Drug Discovery, China Pharmaceutical University, Nanjing, 210009, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Junhao
authors.initials: J
authors.lastname: Xing
authors.forename: Haibo
authors.initials: H
authors.lastname: Cheng
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Shuai
authors.initials: S
authors.lastname: Wang
authors.forename: Jinpei
authors.initials: J
authors.lastname: Zhou
authors.forename: Huibin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000737:chemistry*; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D009593:Nitroimidazoles; D015363:Quinolones
keywords: antibacterial activity; docking study; nitroimidazole; quinolone