7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: synthesis and in vitro biological evaluation as potential antitumor agents

Joëlle Azéma, Brigitte Guidetti, Janique Dewelle, Benjamin Le Calve, Tatjana Mijatovic, Alexander Korolyov, Julie Vaysse, Myriam Malet-Martino, Robert Martino, Robert Kiss

Research output: Contribution to journalArticlepeer-review

Abstract

Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and apoptotic activities in several cancer cell lines. Moreover, several reports have highlighted the interest of increasing the lipophilicity to improve the antitumor efficacy. These studies have led us to synthesize new CP derivatives of various lipophilicities and to evaluate their activity in five human cancer cell lines. With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl) derivatives of CP were prepared that displayed IC(50) values ranging from microM to mM concentrations and are non-toxic in vivo in healthy mice as shown by their maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed higher in vitro antitumor activity than parent CP however this was not dependent on the lipophilicity of the substituent. Among all synthesized derivatives, the most potent were 2 and 6h whose IC(50) values were 10 microM in three (derivative 2) or four (derivative 6h) cancer cell lines.

Original languageEnglish
Pages (from-to)5396-407
Number of pages12
JournalBioorganic & medicinal chemistry
Volume17
Issue number15
DOIs
Publication statusPublished - 2009
Externally publishedYes

Keywords

  • Animals
  • Antineoplastic Agents
  • Cell Line, Tumor
  • Cell Proliferation
  • Ciprofloxacin
  • Humans
  • Maximum Tolerated Dose
  • Mice
  • Neoplasms
  • Piperazines
  • Journal Article

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