Determination of the primary molecular target of 1,2,4-triazole-ciprofloxacin hybrids

Molecules. 2015 Apr 9;20(4):6254-72. doi: 10.3390/molecules20046254.

Abstract

We have synthesized and examined the antibacterial activity, toxicity and affinity towards bacterial type II topoisomerases of a series of 1,2,4-triazole-ciprofloxacin hybrids. A number of these compounds displayed enhanced activity against Gram-positive and Gram-negative bacteria when compared to ciprofloxacin. The toxic concentrations of the obtained derivatives, evaluated on HEK-293 cells using MTT assay, were much higher than concentrations required to produce antibacterial effect. Finally, the results of enzymatic studies showed that the analyzed compounds demonstrated other preferences as regards primary and secondary molecular targets than ciprofloxacin.

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*
  • DNA Topoisomerases, Type II / drug effects
  • Gram-Negative Bacteria / drug effects
  • Gram-Positive Bacteria / drug effects
  • HEK293 Cells
  • Humans
  • Structure-Activity Relationship
  • Topoisomerase II Inhibitors / chemical synthesis
  • Topoisomerase II Inhibitors / chemistry
  • Topoisomerase II Inhibitors / pharmacology*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Topoisomerase II Inhibitors
  • Triazoles
  • 1,2,4-triazole
  • Ciprofloxacin
  • DNA Topoisomerases, Type II