title: Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin.
abstract: Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their toxic side effects and increasing number of resistant pathogens set limits on their use. This review focuses on recent advances concerning quinolones and fluoroquinolones, we will be summarising chemical structure, mode of action, pharmacokinetic properties and toxicity. We will be describing fluoroquinolones introduced in clinical trials, namely avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and non-fluorinated nemonoxacin. These agents have been proved to have enhanced antibacterial effect even against ciprofloxacin resistant pathogens, and found to be well tolerated in both oral and parenteral administrations. These features are going to make them potential antimicrobial agents in the future.
authors.affiliation: Institute of Medical Microbiology, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary. kocsis.bela@med.semmelweis-univ.hu.
authors.forename: Bela
authors.initials: B
authors.lastname: Kocsis
authors.affiliation: Institute of Medical Microbiology, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Domokos
authors.affiliation: Institute of Medical Microbiology, Semmelweis University, Nagyvárad tér 4, Budapest, 1089, Hungary.
authors.forename: D
authors.initials: D
authors.lastname: Szabo
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D027081:DNA Gyrase / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000037:antagonists & inhibitors / Q000378:metabolism; D024881:Drug Resistance, Bacterial / Q000187:drug effects / Q000235:genetics; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D015363:Quinolones; C477891:delafloxacin; C560572:finafloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase; C480202:zabofloxacin; C543520:nemonoxacin
keywords: Chemical structure; Clinical trials; Pharmacokinetics; Quinolones; Safety; Tolerability; Toxicity