Cell-permeable lanthanide-platinum(IV) anti-cancer prodrugs

Dalton Trans. 2021 Jun 29;50(25):8761-8767. doi: 10.1039/d1dt01688a.

Abstract

Platinum compounds are a vital part of our anti-cancer arsenal, and determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group (Ln = Gd, Eu) which demonstrates excellent cellular accumulation and minimal cytotoxicity. Derivatisation enabled access to bimetallic lanthanide-platinum(ii) and lanthanide-platinum(iv) complexes. Luminescence from the europium-platinum(iv) system was quenched, and reduction to platinum(ii) with ascorbic acid resulted in a "switch-on" luminescence enhancement. We used diffusion-based 1H NMR spectroscopic methods to quantify cellular accumulation. The gadolinium-platinum(ii) and gadolinium-platinum(iv) complexes demonstrated appreciable cytotoxicity. A longer delay following incubation before cytotoxicity was observed for the gadolinium-platinum(iv) compared to the gadolinium-platinum(ii) complex. Functionalisation with octanoate ligands resulted in enhanced cellular accumulation and an even greater latency in cytotoxicity.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Drug Screening Assays, Antitumor
  • Gadolinium / chemistry
  • Humans
  • Lanthanoid Series Elements* / chemistry
  • Molecular Structure
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / pharmacology
  • Platinum / chemistry
  • Prodrugs* / chemical synthesis
  • Prodrugs* / chemistry
  • Prodrugs* / pharmacology

Substances

  • Prodrugs
  • Antineoplastic Agents
  • Lanthanoid Series Elements
  • Coordination Complexes
  • Platinum
  • Organoplatinum Compounds
  • Gadolinium