Effect of adenosine modified with a boron cluster pharmacophore on reactive oxygen species production by human neutrophils

Bioorg Med Chem. 2012 Nov 15;20(22):6621-9. doi: 10.1016/j.bmc.2012.09.039. Epub 2012 Sep 25.

Abstract

Methods for the synthesis of adenosine/boron cluster conjugates are proposed and the potential of the obtained derivatives to modulate neutrophil activity, especially reactive oxygen species (ROS) production in vitro, is described. An efficient inhibition of ROS production in activated neutrophils by adenosine modified at the 2'-C and 6-N positions with a para-carborane cluster (C(2)B(10)H(11)) was discovered. The high affinity of the selected compounds for adenosine receptor A(2A) was established. These results are in agreement with the possible involvement of receptor A(2A) in the biological activities of adenosine/boron cluster conjugates. This study extends the range of innovative molecules available for testing as agents affecting inflammatory processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemical synthesis
  • Adenosine / pharmacology
  • Boron / chemistry*
  • Cell Survival / drug effects
  • Humans
  • Neutrophils / cytology
  • Neutrophils / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Receptor, Adenosine A2A / chemistry
  • Receptor, Adenosine A2A / metabolism

Substances

  • Reactive Oxygen Species
  • Receptor, Adenosine A2A
  • Adenosine
  • Boron