title: Design and biological evaluation of novel quinolone-based metronidazole derivatives as potent Cu(2+) mediated DNA-targeting antibacterial agents.
abstract: A series of novel quinolone-based metronidazole derivatives as new type of antimicrobial agents were developed and characterized. Most of them gave good antibacterial activity towards the Gram-positive and negative bacteria. Noticeably, quinolone derivative 3i exhibited low MIC value of 0.25 μg/mL against Pseudomonas aeruginosa, which was even superior to reference drugs Norfloxacin, Ciprofloxacin and Clinafloxacin. The further research revealed that compound 3i could intercalate into P. aeruginosa DNA through copper ion bridge to form a steady 3i-Cu(2+)-DNA ternary complex which might further block DNA replication to exert the powerful bioactivities.
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China.
authors.forename: Kannekanti Vijaya
authors.initials: KV
authors.lastname: Kumar
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China. Electronic address: geng0712@swu.edu.cn.
authors.forename: Rong-Xia
authors.initials: RX
authors.lastname: Geng
authors.affiliation: Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China. Electronic address: zhouch@swu.edu.cn.
authors.forename: Cheng-He
authors.initials: CH
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D002939:Ciprofloxacin / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D004269:DNA, Bacterial / Q000378:metabolism*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005347:Fibroblasts / Q000187:drug effects; D024841:Fluoroquinolones / Q000494:pharmacology; D057809:HEK293 Cells / Q000187:drug effects; D006801:Humans; D008795:Metronidazole / Q000737:chemistry*; D051379:Mice; D008826:Microbial Sensitivity Tests; D058990:Molecular Targeted Therapy / Q000379:methods; D009643:Norfloxacin / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D015363:Quinolones / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D015363:Quinolones; D008795:Metronidazole; D002939:Ciprofloxacin; D003300:Copper; C057477:clinafloxacin; D009643:Norfloxacin
keywords: Antibacterial; DNA; Nitroimidazole; Quinolone