Search for factors affecting antibacterial activity and toxicity of 1,2,4-triazole-ciprofloxacin hybrids

Eur J Med Chem. 2015 Jun 5:97:94-103. doi: 10.1016/j.ejmech.2015.04.058. Epub 2015 Apr 29.

Abstract

A series of 1,2,4-triazole-based compounds was designed as potential antibacterial agents using molecular hybridization approach. The target compounds (23-44) were synthesized by Mannich reaction of 1,2,4-triazole-3-thione derivatives with ciprofloxacin (CPX) and formaldehyde. Their potent antibacterial effect on Gram-positive bacteria was accompanied by similarly strong activity against Gram-negative strains. The toxicity of the CPX-triazole hybrids for bacterial cells was even up to 18930 times higher than the toxicity for human cells. The results of enzymatic studies showed that the antibacterial activity of the CPX-triazole hybrids is not dependent solely on the degree of their affinity to DNA gyrase and topoisomerase IV.

Keywords: 1,2,4-Triazole-3-thiones; Fluoroquinolones; Gyrase DNA; MTT assay; Topoisomerase IV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Ciprofloxacin / chemical synthesis*
  • Ciprofloxacin / chemistry
  • Ciprofloxacin / pharmacology
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • HEK293 Cells
  • Humans
  • Inhibitory Concentration 50
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Anti-Bacterial Agents
  • Triazoles
  • 1,2,4-triazole
  • Ciprofloxacin