Telomerase inhibition by 3'-azido-2', 3'-dideoxynucleoside 5'-triphosphates and telomere shortening in human cultured cells by the corresponding nucleosides

Nucleic Acids Symp Ser (Oxf). 2006:(50):271-2. doi: 10.1093/nass/nrl135.

Abstract

Telomerase is believed to be a good target for the development of antitumor agents. In this study, 3'-azido-2',3'-dideoxy-2-aminoadenosine (AZddAA), 3'-azido-2',3'-dideoxyadenosine (AZddA), 9-(3-azido-2,3-dideoxy-beta-D-ribofuranosyl)-2-aminopurine (AZddAP), 3'-azido-2-chloro-2',3'-dideoxyadenosine (AZddClA) and their triphosphate derivatives were synthesized. Telomerase assay studies showed that the 2-amino group plays an important role in the inhibitory activity of these compounds. In addition, AZddAA was found to cause telomere shortening in of HL60 cells in culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Azides / chemistry
  • Azides / pharmacology
  • Deoxyribonucleotides / chemistry
  • Deoxyribonucleotides / pharmacology*
  • Dideoxynucleosides / chemistry
  • Dideoxynucleosides / pharmacology*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • HL-60 Cells
  • Humans
  • Telomerase / antagonists & inhibitors*
  • Telomere / drug effects*

Substances

  • Antineoplastic Agents
  • Azides
  • Deoxyribonucleotides
  • Dideoxynucleosides
  • Enzyme Inhibitors
  • Telomerase