A cancer specific oxaliplatin-releasing Pt(iv)-prodrug

Dalton Trans. 2018 May 15;47(19):6679-6682. doi: 10.1039/c8dt01458b.

Abstract

We prepared a Pt(iv)-prodrug, which under cancer specific conditions (elevated concentration of reactive oxygen species, ROS) releases a DNA-binding drug oxaliplatin as well as ROS-amplifying drugs p-quinone methide and N-alkylferrocenium. Due to the concerted action of these components, an excellent anticancer effect was achieved: IC50 = 0.4 ± 0.1 μM for human ovarian carcinoma A2780 cells. Importantly, the prodrug was found to be 45-fold less toxic to normal cells (HDFa).

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Molecular Conformation
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Oxaliplatin
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Prodrugs
  • Reactive Oxygen Species
  • Oxaliplatin