A Potent Glucose-Platinum Conjugate Exploits Glucose Transporters and Preferentially Accumulates in Cancer Cells

  • Angew Chem Int Ed Engl. 2016 Feb 12;55(7):2550-4. doi: 10.1002/anie.201510551.
Malay Patra  1 ,  Timothy C Johnstone  1 ,  Kogularamanan Suntharalingam  2 ,  Stephen J Lippard  3
Affiliations
  • 1. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
  • 2. Department of Chemistry, King's College London, London, SE1 1DB, UK.
  • 3. Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA. [email protected].
PMID: 26749149 DOI: 10.1002/anie.201510551
Abstract

Three rationally designed glucose-platinum conjugates (Glc-Pts) were synthesized and their biological activities evaluated. The Glc-Pts, 1-3, exhibit high levels of cytotoxicity toward a panel of Cancer cells. The subcellular target and cellular uptake mechanism of the Glc-Pts were elucidated. For uptake into cells, Glc-Pt 1 exploits both glucose and organic cation transporters, both widely overexpressed in Cancer. Compound 1 preferentially accumulates in and annihilates Cancer, compared to normal epithelial, cells in vitro.

Keywords
antitumor agents; glucose transporters; glycoconjugates; medicinal inorganic chemistry; platinum.
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