Synthesis and biological evaluation of levofloxacin core-based derivatives with potent antibacterial activity against resistant Gram-positive pathogens

Bioorg Med Chem Lett. 2015 Sep 15;25(18):3928-32. doi: 10.1016/j.bmcl.2015.07.044. Epub 2015 Jul 23.

Abstract

A series of C10 non-basic building block-substituted, levofloxacin core-based derivatives were synthesized in 43-86% yield. The antibacterial activity of these new fluoroquinolones was evaluated using a standard broth microdilution technique. The quinolone (S)-9-fluoro-10-(4-hydroxypiperidin-1-yl)-3-methyl-7-oxo-3,7-dihydro-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid L-arginine tetrahydrate exhibited superior antibacterial activity against quinolone-susceptible and resistant strains compared with the clinically used fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin, penicillin, and vancomycin, especially to the methicillin-resistant Staphylococcus aureus clinical isolates, penicillin-resistant Streptococcus pneumoniae clinical isolates, and Streptococcus pyogenes.

Keywords: Levofloxacin core; Methicillin-resistant Staphylococcus aureus; Non-basic building blocks; Penicillin-resistant Streptococcus pneumoniae; Streptococcus pyogenes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Levofloxacin / analogs & derivatives*
  • Levofloxacin / chemical synthesis
  • Levofloxacin / chemistry
  • Levofloxacin / pharmacology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Penicillin Resistance / drug effects
  • Streptococcus pneumoniae / drug effects*
  • Streptococcus pyogenes / drug effects*
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Levofloxacin