Synthesis and biological evaluation of clitocine analogues as adenosine kinase inhibitors

Bioorg Med Chem Lett. 2001 Sep 17;11(18):2419-22. doi: 10.1016/s0960-894x(01)00454-1.

Abstract

Adenosine kinase (AK) is the primary enzyme responsible for adenosine metabolism. Inhibition of AK effectively increases extracellular adenosine concentrations and represents an alternative approach to enhance the beneficial actions of adenosine as compared to direct-acting receptor agonists. Clitocine (3), isolated from the mushroom Clitocybe inversa, has been found to be a weak inhibitor of AK. We have prepared a number of analogues of clitocine in order to improve its potency and demonstrated that 5'-deoxy-5'-amino-clitocine (7) improved AK inhibitory potency by 50-fold.

MeSH terms

  • Adenosine Kinase / antagonists & inhibitors*
  • Animals
  • Biochemistry / methods
  • Drug Design
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Inhibitory Concentration 50
  • Pyrimidine Nucleosides / chemistry*
  • Pyrimidine Nucleosides / pharmacology*
  • Rats
  • Structure-Activity Relationship

Substances

  • 5'-deoxy-5'-amino-clitocine
  • Enzyme Inhibitors
  • Pyrimidine Nucleosides
  • clitocine
  • Adenosine Kinase