Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells

J Photochem Photobiol B. 2014 Nov:140:57-68. doi: 10.1016/j.jphotobiol.2014.07.006. Epub 2014 Jul 22.

Abstract

The photobehavior of ciprofloxacin, lomefloxacin and ofloxacin fluoroquinolones was investigated using several in vitro methods to assess their cytotoxic, antiproliferative, and genotoxic potential against two human cancer cell lines. We focused our attention on the possible relationship between their chemical structure, O₂ partial pressure and photobiological activity on cancer cells. The three molecules share the main features of most fluoroquinolones, a fluorine in 6 and a piperazino group in 7, but differ at the key position 8, unsubstituted in ciprofloxacin, a fluorine in lomefloxacin and an alkoxy group in ofloxacin. Studies in solution show that ofloxacin has a low photoreactivity; lomefloxacin reacts via aryl cation, ciprofloxacin reacts but not via the cation. In our experiments, ciprofloxacin and lomefloxacin showed a high and comparable potential for photodamaging cells and DNA. Lomefloxacin appeared the most efficient molecule in hypoxia, acting mainly against tumour cell proliferation and generating DNA plasmid photocleavage. Although our results do not directly provide evidence that a carbocation is involved in photodamage induced by lomefloxacin, our data strongly support this hypothesis. This may lead to new and more efficient anti-tumour drugs involving a cation in their mechanism of action. This latter acting independently of oxygen, can target hypoxic tumour tissue.

Keywords: Anticancer drugs; Apoptosis; DNA damage; Fluoroquinolones; UVA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Cycle Checkpoints / drug effects
  • Cell Cycle Checkpoints / radiation effects
  • Cell Hypoxia
  • Cell Line, Tumor
  • Ciprofloxacin / chemistry
  • Ciprofloxacin / toxicity
  • DNA Damage / drug effects
  • DNA Damage / radiation effects
  • Fluoroquinolones / chemistry*
  • Fluoroquinolones / toxicity
  • HeLa Cells
  • Humans
  • Oxygen / chemistry*
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / toxicity
  • Plasmids / drug effects
  • Plasmids / metabolism
  • Singlet Oxygen / chemistry
  • Singlet Oxygen / metabolism
  • Structure-Activity Relationship
  • Ultraviolet Rays

Substances

  • Fluoroquinolones
  • Photosensitizing Agents
  • Singlet Oxygen
  • Ciprofloxacin
  • lomefloxacin
  • Oxygen