Synthetic nucleosides and nucleotides. 40. Selective inhibition of eukaryotic DNA polymerase alpha by 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino) adenine 5'-triphosphate (BuAaraATP) and its 2'-up azido analog: synthesis and enzymatic evaluations

Nucleosides Nucleotides. Jan-Mar 1998;17(1-3):487-501. doi: 10.1080/07328319808005193.

Abstract

Starting from 2',3',5'-tri-O-acetyl-2-iodoadenosine, 9-(beta-D-arabinofuranosyl)-2-(p-n-butylanilino)adenine and its 2'(S)-azido counterparts were synthesized in seven steps. These exhibited only moderate growth-inhibitory effects against mouse leukemic P388 cells (IC50 = 13-24 microM), although 5'-triphosphate derivatives showed strong and selective inhibitory action on calf thymus DNA polymerase alpha, but not on beta- and epsilon-polymerases from eukaryotes.

MeSH terms

  • Adenine / analogs & derivatives
  • Adenosine / analogs & derivatives
  • Adenosine Triphosphate / analogs & derivatives*
  • Animals
  • Azo Compounds / chemical synthesis*
  • Cell Division / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Mice
  • Nucleic Acid Synthesis Inhibitors*
  • Nucleosides / chemical synthesis*
  • Nucleotides / chemical synthesis*
  • Tumor Cells, Cultured

Substances

  • Azo Compounds
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
  • Nucleosides
  • Nucleotides
  • Adenosine Triphosphate
  • Adenine
  • Adenosine