Analysis of positions and substituents on genotoxicity of fluoroquinolones with quantitative structure-activity relationship and 3D Pharmacophore model

Ecotoxicol Environ Saf. 2017 Feb;136:111-118. doi: 10.1016/j.ecoenv.2016.10.036. Epub 2016 Nov 8.


The genotoxicity values of 21 quinolones were studied to establish a quantitative structure-activity relationship model and 3D Pharmacophore model separately for screening essential positions and substituents that contribute to genotoxicity of fluoroquinolones (FQs). A full factor experimental design was performed to analyze the specific main effect and second-order interaction effect of different positions and substituents on genotoxicity, forming a reasonable modification scheme which was validated on typical FQ with genotoxicity and efficacy data. Four positions (1, 5, 7, 8) were screened finally to form the full factorial experimental design which contained 72 congeners in total, illustrating that: the dominant effect of 5 and 7-positions on genotoxicity of FQs is main effect; meanwhile the effect of 1 and 8-positions is a second-order interaction effect; two adjacent positions always have stronger second-order interaction effect and lower genotoxicity; the obtained modification scheme had been validated on typical FQ congeners with the modified compound has a lower genotoxicity, higher synthesis feasibilities and efficacy.

Keywords: Fluoroquinolones; Full factorial experimental design; Genotoxicity; Pharmacophore model; Quantitative structure-activity relationship.

MeSH terms

  • DNA Damage*
  • Environmental Pollutants / chemistry
  • Environmental Pollutants / toxicity*
  • Fluoroquinolones / chemistry
  • Fluoroquinolones / toxicity*
  • Models, Theoretical
  • Mutagenicity Tests
  • Mutagens / chemistry
  • Mutagens / toxicity*
  • Quantitative Structure-Activity Relationship


  • Environmental Pollutants
  • Fluoroquinolones
  • Mutagens