Design, synthesis and enzymatic activity of highly selective human mitochondrial thymidine kinase inhibitors

Bioorg Med Chem Lett. 2001 May 21;11(10):1329-32. doi: 10.1016/s0960-894x(01)00207-4.

Abstract

Highly selective arabinofuranosyl nucleosides, which inhibit the mitochondrial thymidine kinase (TK-2) without affecting the closely related herpes simplex virus type 1 thymidine kinase (HSV-1 TK), varicella-zoster virus thymidine kinase (VZV-TK), cytosolic thymidine kinase (TK-1) or the multifunctional Drosophila melanogaster deoxyribonucleoside kinase (Dm-dNK), have been obtained. SAR studies indicate a close relation between the length of the substituent at the 2' position of the arabinofuranosyl moiety and the inhibitory activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabinonucleosides / chemical synthesis*
  • Arabinonucleosides / pharmacology
  • Catalytic Domain
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Mitochondria / enzymology*
  • Models, Molecular
  • Structure-Activity Relationship
  • Thymidine Kinase / antagonists & inhibitors*
  • Viral Proteins / antagonists & inhibitors

Substances

  • Arabinonucleosides
  • Enzyme Inhibitors
  • Viral Proteins
  • thymidine kinase 2
  • Thymidine Kinase