Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin

Ann Clin Microbiol Antimicrob. 2016 May 23;15(1):34. doi: 10.1186/s12941-016-0150-4.

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.

Keywords: Chemical structure; Clinical trials; Pharmacokinetics; Quinolones; Safety; Tolerability; Toxicity.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology
  • Clinical Trials as Topic
  • DNA Gyrase / metabolism
  • DNA Topoisomerase IV / antagonists & inhibitors
  • DNA Topoisomerase IV / metabolism
  • Drug Resistance, Bacterial / drug effects
  • Drug Resistance, Bacterial / genetics
  • Fluoroquinolones / chemical synthesis
  • Fluoroquinolones / pharmacokinetics*
  • Fluoroquinolones / pharmacology
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / growth & development
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / growth & development
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quinolones / chemical synthesis
  • Quinolones / pharmacokinetics*
  • Quinolones / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Quinolones
  • delafloxacin
  • finafloxacin
  • DNA Topoisomerase IV
  • DNA Gyrase
  • zabofloxacin
  • nemonoxacin