New fluoroquinolone compounds with endo-nortropine derivatives at C-7 position show antibacterial activity against fluoroquinolone-resistant strains of Staphylococcus aureus

Chem Biol Drug Des. 2019 Sep;94(3):1626-1633. doi: 10.1111/cbdd.13513. Epub 2019 Jul 10.

Abstract

A series of new fluoroquinolone analogs (3-18) were prepared, in three steps, by substituting chloro esters and esters with cyclic amines on the C-7 endo-nortropine derivatives of difluoroquinolone acid. All the synthesized compounds displayed good MIC against the Staphylococcus aureus when initially screened for Escherichia coli, S. aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. The molecules were further evaluated for their antibacterial activity against fluoroquinolone-resistant strains of S. aureus and for cytotoxic assay. Based on the results, five of the sixteen compounds displayed the potential to be developed further for treatment against fluoroquinolone-resistant strains of S. aureus.

Keywords: N-methylpiperazine; levofloxacin; morpholine; nalidixic acid; piperidine.

MeSH terms

  • Amines / chemistry
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Bacterial Infections / drug therapy*
  • Drug Evaluation, Preclinical
  • Drug Resistance, Bacterial
  • Esters / chemistry
  • Fluoroquinolones / chemical synthesis*
  • Fluoroquinolones / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Nortropanes / chemistry*
  • Structure-Activity Relationship

Substances

  • Amines
  • Anti-Bacterial Agents
  • Esters
  • Fluoroquinolones
  • Nortropanes