Copper-free click-chemistry platform to functionalize cisplatin prodrugs

Chemistry. 2014 Jun 2;20(23):6861-5. doi: 10.1002/chem.201402573. Epub 2014 Apr 23.

Abstract

The ability to rationally design and construct a platform technology to develop new platinum(IV) [Pt(IV)] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well-defined chemistry is critical for discovering new platinum-based therapeutics. With limited numbers of possibilities considering the sensitivity of Pt(IV) centers, we used a strain-promoted azide-alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single Pt(IV) precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated.

Keywords: cancer; cisplatin; click chemistry; nanoparticles; prodrugs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alkynes / chemistry
  • Antineoplastic Agents / pharmacology
  • Azides / chemistry
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / chemistry*
  • Cisplatin / pharmacology
  • Click Chemistry
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacology
  • Copper / chemistry*
  • Cycloaddition Reaction
  • Drug Carriers / chemistry
  • Humans
  • Nanostructures / chemistry
  • Oxidation-Reduction
  • Platinum / chemistry
  • Prodrugs / chemistry*
  • Prodrugs / pharmacology

Substances

  • Alkynes
  • Antineoplastic Agents
  • Azides
  • Coordination Complexes
  • Drug Carriers
  • Prodrugs
  • Platinum
  • Copper
  • Cisplatin