Design, synthesis, molecular docking, anti-Proteus mirabilis and urease inhibition of new fluoroquinolone carboxylic acid derivatives

Bioorg Chem. 2017 Feb:70:1-11. doi: 10.1016/j.bioorg.2016.11.002. Epub 2016 Nov 9.

Abstract

New hydroxamic acid, hydrazide and amide derivatives of ciprofloxacin in addition to their analogues of levofloxacin were prepared and identified by different spectroscopic techniques. Some of the prepared compounds revealed good activity against the urease splitting bacteria, Proteus mirabilis. The urease inhibitory activity was investigated using indophenol method. Most of the tested compounds showed better activity than the reference acetohydroxamic acid (AHA). The ciprofloxacin hydrazide derivative 3a and levofloxacin hydroxamic acid 7 experienced the highest activity (IC50=1.22μM and 2.20μM, respectively). Molecular docking study revealed high spontaneous binding ability of the tested compounds to the active site of urease.

Keywords: Antibacterial; Docking; Fluoroquinolones; Hydroxamic acid; Urease inhibitors.

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Catalytic Domain / drug effects
  • Drug Discovery
  • Fluoroquinolones / chemistry*
  • Fluoroquinolones / pharmacology*
  • Humans
  • Hydroxamic Acids / chemistry
  • Hydroxamic Acids / pharmacology
  • Molecular Docking Simulation
  • Proteus Infections / drug therapy
  • Proteus Infections / microbiology
  • Proteus mirabilis / drug effects
  • Proteus mirabilis / enzymology*
  • Urease / antagonists & inhibitors*
  • Urease / chemistry
  • Urease / metabolism

Substances

  • Anti-Bacterial Agents
  • Fluoroquinolones
  • Hydroxamic Acids
  • acetohydroxamic acid
  • Urease