Polyoxometalates--a new class of potent ecto-nucleoside triphosphate diphosphohydrolase (NTPDase) inhibitors

Bioorg Med Chem Lett. 2006 Dec 1;16(23):5943-7. doi: 10.1016/j.bmcl.2006.09.003. Epub 2006 Sep 25.

Abstract

Polyoxotungstates were identified as potent inhibitors of NTPDases1, 2, and 3. The most potent compound was K(6)H(2)[TiW(11)CoO(40)], exhibiting K(i) values of 0.140 microM (NTPDase1), 0.910 microM (NTPDase2), and 0.563 microM (NTPDase3). One of the compounds, (NH(4))(18)[NaSb(9)W(21)O(86)], was selective for NTPDases2 and 3 versus NTPDase1. NTPDase inhibition might contribute to the described biological effects of polyoxometalates, including their anti-cancer activity.

MeSH terms

  • Adenosine Triphosphatases / antagonists & inhibitors*
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Antigens, CD / metabolism
  • Apyrase / antagonists & inhibitors*
  • Apyrase / metabolism
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / classification*
  • Enzyme Inhibitors / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Pyrophosphatases / antagonists & inhibitors*
  • Pyrophosphatases / metabolism
  • Rats
  • Structure-Activity Relationship

Substances

  • Antigens, CD
  • Enzyme Inhibitors
  • Adenosine Triphosphatases
  • Pyrophosphatases
  • ectoATPase
  • nucleoside-triphosphate diphosphohydrolase 3
  • Apyrase
  • CD39 antigen